Methods and systems for coating an oral surface

ABSTRACT

A coating system and method are described. In some embodiments, a system may include a composition. The composition may include one or more bridged polycyclic compounds. At least one of the bridged polycyclic compounds may include at least two cyclic groups, and at least two of the cyclic groups may include quaternary ammonium moieties. In some embodiments, a method may include applying a coating to an oral surface. The coating may be antimicrobial. A coating may include antimicrobial bridged polycyclic compounds. Bridged polycyclic compounds may include quaternary ammonium compounds. Bridged polycyclic compounds based coating systems may impart self-cleaning properties to a surface (e.g., a tooth surface).

PRIORITY CLAIM

This application claims priority to U.S. Provisional Patent ApplicationNo. 60/749,540 entitled “ANTIMICROBIAL FILMS AND COATINGS” filed on Dec.12, 2005, U.S. Provisional Patent Application No. 60/755,292 entitled“ANTIMICROBIAL AND/OR SELF-CLEANING FILMS” filed on Dec. 30, 2005, andU.S. Provisional Patent Application No. 60/756,401 entitled “METHODS ANDSYSTEMS FOR PREPARING ANTIMICROBIAL COATINGS” filed on Jan. 5, 2006, allof which are incorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present disclosure generally relates to self-cleaning and/orantimicrobial compositions. More particularly, the disclosure generallyrelates to systems and methods for the customizable formation ofantimicrobial compositions. Further, the disclosure generally relates tosystems and methods for preparation of films and coatings using theprepared antimicrobial compositions.

2. Description of the Relevant Art

Bacteria exist in a variety of locations—in water, soil, plants,animals, and humans. Bacteria may transfer from person to person, amonganimals and people, from animals to animals, and through water and thefood chain. Most bacteria do little or no harm, and some are even usefulto humans. However, others are capable of causing disease. The samebacteria may have different effects on different parts of the host body.For example, S. aureus on the skin may be generally harmless, but whenthey enter the bloodstream they may cause disease.

An antimicrobial may be generally defined as anything that may kill orinhibit the growth of microbes (e.g., high heat or radiation or achemical). Microbes may be generally defined as a minute life form, amicroorganism, especially a bacterium that causes disease.Antimicrobials may be grouped into three broad categories: antimicrobialdrugs, antiseptics, and disinfectants. Antimicrobial drugs may be usedin relatively low concentrations in or upon the bodies of organisms toprevent or treat specific bacterial diseases without harming theorganism. They are also used in agriculture to enhance the growth offood animals. Unlike antimicrobial drugs, antiseptics and disinfectantsare usually nonspecific with respect to their targets—they kill orinhibit a variety of microbes. Antiseptics may be used topically in oron living tissue. Disinfectants may be used on objects or in water.

Antimicrobial resistance may be generally described as a feature of somebacteria that enables them to avoid the effects of antimicrobial agents.Bacteria may possess characteristics that allow them to survive a suddenchange in climate, the effects of ultraviolet light from the sun, and/orthe presence of an antimicrobial chemical in their environment. Somebacteria are naturally resistant. Other bacteria acquire resistance toantimicrobials to which they once were susceptible.

The development of resistance to an antimicrobial is complex.Susceptible bacteria may become resistant by acquiring resistance genesfrom other bacteria or through mutations in their own genetic material(DNA). Once acquired, the resistance characteristic is passed on tofuture generations and sometimes to other bacterial species.

Antimicrobials have been shown to promote antimicrobial resistance in atleast three ways: through (1) encouraging the exchange of resistantgenes between bacteria, (2) favoring the survival of the resistantbacteria in a mixed population of resistant and susceptible bacteria,and (3) making people and animals more vulnerable to resistantinfection. Although the contribution of antimicrobials in promotingresistance has most often been documented for antimicrobial drugs, thereare also reports of disinfectant use contributing to resistance andconcerns about the potential for antiseptics to promote resistance. Forexample, in the case of disinfectants, researchers have found thatchlorinated river water contains more bacteria that are resistant tostreptomycin than does non-chlorinated river water. Also, it has beenshown that some kinds of Escherichia coli (E. coli) resist triclosan (anantiseptic used in a variety of products, including soaps andtoothpaste). This raises the possibility that antiseptic use couldcontribute to the emergence of resistant bacteria.

While antimicrobials are a major factor in the development ofresistance, many other factors are also involved, including for examplethe nature of the specific bacteria and antimicrobial involved, the waythe antimicrobial is used, characteristics of the host, andenvironmental factors. Therefore, the use of antimicrobials does notalways lead to resistance.

The Staphylococcus aureus bacterium (S. aureus), one of the most commoncauses of infections worldwide, has long been considered treatable withantimicrobial drugs. Recently, however, a number of S. aureus infectionswere found that resisted most available antimicrobials, includingvancomycin, the last line of treatment for these and some otherinfections. For example, several years ago in Japan, a four-month-oldinfant who had developed an S. aureus infection following surgery, diedafter a month of treatments with various antimicrobials, includingvancomycin. About a year later, three elderly patients in the UnitedStates with multiple chronic conditions were infected with this type ofS. aureus, now known as vancomycin intermediate-resistant Staphylococcusaureus (VISA). They were treated with numerous antimicrobials for anextended period of time and eventually died, but it is unclear what roleVISA played in their deaths. More recently, a middle-aged cancer patientin Hong Kong was admitted to a hospital with a fever and died despitetwo weeks of treatment for VISA.

Antimicrobials are recognized as major contributors in the developmentof antimicrobial resistance. There are many kinds of antimicrobials,varying in how they are used and in the agencies that have jurisdictionover them. The EPA is in fact conducting a reexamination of allpesticides (and antimicrobials), which received regulatory approvalbefore 1984. In addition, the World Health Organization (WHO) has alsorepositioned itself to deal with this issue.

The causes for antimicrobial resistance are believed to bemulti-factoral. In the case of antibiotics, it has been well documentedthat resistance is mainly caused by continued over reliance on andimprudent use of these antimicrobial agents. Increasing evidence isbeing obtained suggesting that the same may be true for the emergence ofbiocide resistance. There is increasing concern about possiblecross-resistance of antibiotics and biocides due to common resistancemechanisms. The consequence of continued exposure to antimicrobials isan increase of bacteria that are intrinsically resistant toantimicrobials or have acquired resistance mechanisms to thesesubstances.

Bacterial resistance mechanisms have been mostly determined forantibiotics and include: 1) exclusion from the cell (e.g., by the outermembrane); 2) enzymatic inactivation; 3) target alterations; and 4)active efflux from the cell. Similar resistance mechanisms are alsoinvolved in biocide resistance. Although exclusion from the cell due toreduced outer membrane impermeability was thought to play a key role inthe intrinsic resistance of several common bacteria (e.g., P.aeruginosa) to many antimicrobial compounds, this is now attributed tosynergy between a low-permeability outer membrane and active efflux fromthe cell. Some bacteria promote acquired multi-drug resistance as aconsequence of hyper expression of the efflux genes by mutationalevents. In addition to antibiotics, these pumps export biocides, dyes,detergents, metabolic inhibitors, organic solvents and moleculesinvolved in bacterial cell-cell communication. A discussion ofmechanisms of antimicrobial resistance may be found in Schweizer “Effluxas a mechanism of resistance to antimicrobials in Pseudomonas aeruginosaand related bacteria: unanswered questions” Genet. Mol. Res., 2(1):48-62 (Mar. 31, 2003), which is incorporated by reference as if fullyset forth herein.

Concern about possible cross-resistance of antibiotics and biocides dueto common resistance mechanisms may be further accentuated when themechanism of several different antimicrobials are compared. For example,the antimicrobial effects of silver salts have been noticed sinceancient times, and today, silver is used to control bacterial growth ina variety of applications, including dental work, catheters, and burnwounds. Added at high (i.e., millimolar) concentrations, Ag⁺ ionsinhibit a number of enzymatic activities, reacting with electron donorgroups, especially sulfhydryl groups. However, research in the past fewyears of the molecular mechanism of the bactericidal effect of muchlower (e.g., micromolar) concentrations of Ag⁺ ions points toward adifferent mechanism.

The addition of low micromolar concentrations of Ag⁺ to inside-outmembrane vesicles of V. cholerae induced a total collapse of both ΔpHand Δψ irrespective of the presence of Na⁺ ions. This effect of Ag⁺ wasindependent of the presence of the Na⁺-translocating NQR, known as aspecific target for submicromolar Ag⁺, suggesting that the otherAg⁺-modified membrane proteins (or perhaps the Ag⁺-modified phospholipidbilayer itself) may cause the H⁺ leakage, thus explaining the broadspectrum of the antimicrobial activity of Ag⁺ ions. It is conceivablethat the bactericidal action of these concentrations of Ag⁺ in V.cholerae is not mediated by a specific target but is due to the H⁺leakage occurring through virtually any Ag⁺-modified membrane protein orperhaps through the Ag⁺-modified phospholipid bilayer itself. In theabsence of Ag⁺ resistance determinants (encoding pumps capable ofefficient expelling of the Ag⁺ ion), this would result in a completedeenergization of the membrane. Taking into account the well-documentedcrucial importance of the transmembrane proton gradient in overallmicrobial metabolism, it seems inevitable that the protonophore-likeeffect of Ag⁺ described here should result in cell death. A discussionof the antimicrobial properties of silver may be found in Dibrov et al.“Chemiosmotic Mechanism of Antimicrobial Activity of Ag⁺ in Vibriocholerae” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, August 2002, p.2668-2670, which is incorporated by reference as if fully set forthherein.

The antimicrobial effects of titanium dioxide have been known for quitesome time and it is used to control bacteria activity. When titaniumdioxide (TiO₂) is irradiated with near-UV light, this semiconductorexhibits strong bactericidal activity. Evidence has been presented thatappears to show that the lipid peroxidation reaction is the underlyingmechanism of death of Escherichia coli K-12 cells that are irradiated inthe presence of the TiO₂ photocatalyst. Using production ofmalondialdehyde (MDA) as an index to assess cell membrane damage bylipid peroxidation, it was observed that there was an exponentialincrease in the production of MDA, whose concentration reached 1.1 to2.4 nmol·mg (dry weight) of cells⁻¹ after 30 min of illumination, andthat the kinetics of this process paralleled cell death. Under theseconditions, concomitant losses of 77 to 93% of the cell respiratoryactivity were also detected, as measured by both oxygen uptake andreduction of 2,3,5-triphenyltetrazolium chloride from succinate as theelectron donor. The occurrence of lipid peroxidation and thesimultaneous losses of both membrane-dependent respiratory activity andcell viability depended strictly on the presence of both light and TiO₂.It was theorized that TiO₂ photocatalysis promoted peroxidation of thepolyunsaturated phospholipid component of the lipid membrane initiallyand induced major disorder in the E. coli cell membrane. Subsequently,essential functions that rely on intact cell membrane architecture, suchas respiratory activity, were lost, and cell death was inevitable. Adiscussion of the antimicrobial properties of titanium dioxide may befound in Maness et al. “Bactericidal Activity of Photocatalytic TiO₂Reaction: toward an Understanding of Its Killing Mechanism” APPLIED ANDENVIRONMENTAL MICROBIOLOGY, September 1999, p. 4094-4098, which isincorporated by reference as if fully set forth herein.

Phenol and its derivatives exhibit several types of bactericidal action.At higher concentrations, the compounds penetrate and disrupt the cellwall and precipitate cell proteins. Generally, gram-positive bacteriaare more sensitive than gram-negative bacteria, which in turn are moresensitive than mycobacteria. The initial reaction between a phenolicderivative and bacteria involves binding of the active phenol species tothe cell surface. Once the active has bound to the exterior of the cell,it needs to penetrate to its target sites-either by passive diffusion(gram-positive) or by the hydrophobic lipid bilayer pathway(gram-negative). One of the initial events to occur at the cytoplasmicmembrane is the inhibition of membrane bound enzymes. The next level inthe damage to the cytoplasmic membrane is the loss in the membrane'sability to act as a permeability barrier. There is limited informationregarding the action of phenolics against viruses. The molecularmechanisms probably do not differ from those that occur in bacteria.Phenols act at the germination stage of bacterial spore development;however, this effect is reversible-therefore the sporicidal activity ofphenolic compounds is low. As with many disinfectants, the activity ofphenols is highly formulation dependant and affected by factors such astemperature, concentration, pH and the presence of organic matter.

Although the mode of action of quaternary ammonium compounds has not yetbeen completely described in detail, there are definitive explanationsof the antimicrobial mode of action of cationic disinfectants ingeneral.

One of the main considerations in examining the mode of action is thecharacterization of quaternary ammonium compounds as cationicsurfactants. This class of chemical reduces the surface tension atinterfaces, and is attracted to negatively charged surfaces, includingmicroorganisms. Quaternary ammonium compounds denature the proteins ofthe bacterial or fungal cell, affect the metabolic reactions of the celland allow vital substances to leak out of the cell, finally causingdeath.

Classification of the “generation” of quaternary ammonium compounds maybe confusing. The most current definitions of the different generationsof quaternary ammonium compounds are as follows:

-   -   First Generation: Benzalkonium chlorides (example: Benzalkonium        chloride). First generation quaternary ammonium compounds have        the lowest relative biocidal activity and are commonly used as        preservatives.    -   Second Generation: Substituted benzalkonium chlorides (example:        alkyl dimethyl benzyl ammonium chloride). The substitution of        the aromatic ring hydrogens with chlorine, methyl and/or ethyl        groups resulted in second generation quaternary ammonium        compounds with high biocidal activity.    -   Third Generation: “Dual Quaternary ammonium compounds” (example:        contain an equal mixture of alkyl dimethyl benzyl ammonium        chloride+alkyl dimethyl ethylbenzyl ammonium chloride). This        mixture of two specific quaternary ammonium compounds resulted        in a dual quaternary ammonium compound offering increased        biocidal activity, stronger detergency, and increased safety to        the user (relative lower toxicity).    -   Fourth Generation: “Twin or Dual Chain Quaternary ammonium        compounds”—dialkylmethyl amines (example: didecyl dimethyl        ammonium chloride or dioctyl dimethyl ammonium chloride). Fourth        generation quaternary ammonium compounds are superior in        germicidal performance, lower foaming, and have an increased        tolerance to protein loads and hard water.    -   Fifth Generation: Mixtures of fourth generation quaternary        ammonium compounds with second-generation quaternary ammonium        compounds (example: didecyl dimethyl ammonium chloride+alkyl        dimethyl benzyl ammonium chloride). Fifth generation quaternary        ammonium compounds have an outstanding germicidal performance,        they are active under more hostile conditions and are safer to        use.

This information is general in principle. For example, it may not alwaysbe the case that a disinfectant with a fifth-generation quaternaryammonium compound is better than one with a third-generation quaternaryammonium compound. The non-germicide components of a disinfectant alsohave an impact on overall performance. Quaternary ammonium compounds areextremely sensitive to hard water, and usually require a chelant in theformula to obtain efficacy in these conditions. Although regarded asstandard by one authority, the quaternary ammonium compound generationdefinitions given above may differ from those found elsewhere.Regardless, the examples given should give one a relative understandingof the evolution of quaternary germicides.

Glutaraldehyde-protein interactions indicate an effect of the dialdehydeon the surface of bacterial cells. Many of the studies indicate apowerful binding of the aldehyde to the outer cell layers. Because ofthis reaction in the outer structures of the cell, there is aninhibitory effect on RNA, DNA, and protein synthesis as a result.

In reacting with bacterial spores, studies have shown that acidglutaraldehyde could interact at the spores' surface and remain there,whereas alkaline glutaraldehyde could penetrate the spore. Thus, therole of the activator: an alkalinizing agent in facilitating penetrationand interaction of glutaraldehyde with components of the spore cortex orcore. Inhibition of germination, spore swelling, mycelial growth, andsporulation in fungal species at varying concentrations has beendemonstrated. The principal structural wall component of many molds andyeast is chitin, which resembles the peptidoglycan of bacteria and isthus a potentially reactive site for glutaraldehyde action. In viruses,the main targets for glutaraldehyde are nucleic acid, proteins, andenvelope constituents. The established reactivity of glutaraldehyde withproteins suggests that the viral capsid or viral-specific enzymes arevulnerable to glutaraldehyde treatment.

Ortho-phthalaldehyde is a claimed alternative aldehyde that is currentlyunder investigation. Unlike glutaraldehyde, ortho-phthalaldehyde isodorless, stable, and effective over a wide pH range. It has beenproposed that, because of the lack of alpha-hydrogens,ortho-phthalaldehyde remains in its active form at alkaline pH.

EDTA and other chelating agents are often added to the germicide formulato aid in activity in hard water conditions. These ingredients also addto the antimicrobial activity by chelating magnesium and calcium in theorganism. EDTA has been shown to boost the effect of antimicrobialactivity against gram-negative organisms such as Pseudomonas aeruginosa.

Many antimicrobials function by attacking and disrupting the cellmembrane causing the microbe to “bleed” to death. Other antimicrobialsfunction by penetrating the cell membrane and subsequently inhibitingone or more functions within the cell. Therefore microbial adaptations,such as reduced outer membrane impermeability and active efflux from thecell, may reduce the effectiveness of many known and commonly usedantimicrobials. Antimicrobial resistance has increased due to the overuse and misuse of antimicrobials. Part of the problem has beenattributed to antimicrobials which, due to their design, leach into theenvironment excessively overexposing microbes in the environmentpromoting antimicrobial resistance.

New antimicrobials are required to combat the new antimicrobialresistant microbes. New antimicrobials may be effective verses microbeswhich are currently resistant to currently known antimicrobials. Newantimicrobials may resist leaching off into the environment beyond apredetermined amount to inhibit polluting the environment unnecessarily.

SUMMARY

For the reasons stated above new antimicrobials are required to combatthe new antimicrobial resistant microbes. Antimicrobial compositions aredescribed. More particularly, systems and methods for the customizableformation of antimicrobial compositions for coating surfaces aredescribed. Further, systems and methods for the preparation of films andcoatings using the prepared antimicrobial compositions are described.

In some embodiments, a protective coating composition may include acompound. A compound may include a bridged polycyclic compound. Abridged polycyclic compound may be a cavitand. Portions of the bridgedpolycyclic compound may include two or more quaternary ammoniummoieties. The coating composition may be antimicrobial.

In some embodiments, a protective coating composition may beantimicrobial.

In some embodiments, a protective coating composition may beself-cleaning.

In some embodiments, a chemical composition may include a chemicalcompound, wherein the chemical compound has a general structure (I):

Each R¹ may be independently an alkyl group, a substituted alkyl group,an aryl group, a substituted aryl group, N, N⁺R³, a heterocycle group,or a substituted heterocycle group. Each R² may be independently analkyl group, a substituted alkyl group, an aryl group, a substitutedaryl group, a heterocycle group, a substituted heterocycle group, acovalent bond, or an alkene. Each R³ may be independently an alkylgroup, a substituted alkyl group, an aryl group, a substituted arylgroup, a heterocycle group, a substituted heterocycle group, an alkene,an ether, a PEG, or a PEI. Each R⁴ may be independently an alkyl group,a substituted alkyl group, an aryl group, a substituted aryl group, aheterocycle group, a substituted heterocycle group, an ether, an amide,an alcohol, an ester, a sulfonamide, a sulfanilamide, or an alkene. Zmay include at least one bridge. At least one of the bridges may be—R²—N⁺R³ ₂—R⁴—N⁺R³ ₂—R²—, —R²—NR³—R⁴—N⁺R³ ₂—R²—, —R²—NR³—R⁴—NR³—R²—, or—R²—N═R⁴═N—R²—. Each bridge may independently couples R¹ to R¹. X mayinclude one or more negatively charged counter ions.

In some embodiments, a chemical composition may include one or morepolymerizable compounds.

In some embodiments, a chemical composition may include one or morepolymerizable compounds, wherein the chemical composition is configuredsuch that, when the chemical composition is applied to a surface andcured, then at least a portion of the composition forms an antimicrobialcoating over at least a portion of the surface.

In some embodiments, at least one R³ may include at least one quaternaryammonium moiety.

In some embodiments, at least one R³ may include at least one phenolmoiety.

In some embodiments, at least one R³ may include at least one azolemoiety.

In some embodiments, at least one R³ is a benzyl group.

In some embodiments, at least one R³ is a chloro substituted benzylgroup.

In some embodiments, at least one R³ is a benzyl group, and wherein atleast one R³ is a C6 alkyl group or a C6 substituted alkyl group.

In some embodiments, at least one R³ is a chloro substituted benzylgroup, and wherein at least one R³ is a C6 alkyl group or a C6substituted alkyl group.

In some embodiments, at least one R³ is a methoxy substituted benzylgroup, and wherein at least one R³ is a C6 alkyl group or a C6substituted alkyl group.

In some embodiments, at least one R³ is a alkoxy substituted benzylgroup, and wherein at least one R³ is a C6 alkyl group or a C6substituted alkyl group.

In some embodiments, at least one R³ is a hydroxyl substituted benzylgroup, and wherein at least one R³is a C6 alkyl group or a C6substituted alkyl group.

In some embodiments, at least one R³is an ammonium substituted benzylgroup, and wherein at least one R³is a C6 alkyl group or a C6substituted alkyl group.

In some embodiments, at least one R³is a polyether substituted benzylgroup, and wherein at least one R³ is a C6 alkyl group or a C6substituted alkyl group.

In some embodiments, at least one R³is a benzyl group, and wherein atleast one R³ is a C6 alkyl group or a C6 substituted imidazole group.

In some embodiments, at least one R³ is a methyl group, and wherein atleast one R³is a C6 alkyl group or a C6 substituted alkyl group.

In some embodiments, at least one R³ is a methyl group, and wherein atleast one R³ is a C5-C7 alkyl group or a C5-C7 substituted alkyl group.

In some embodiments, at least one X is an anion. In some embodiments, atleast one X is a polymer. In some embodiments, at least one X is amonomer. In some embodiments, at least one X is a halogen. In someembodiments, at least one X is iodine, bromine, or chlorine. In someembodiments, at least one X contains boron. In some embodiments, atleast one X is a borate. In some embodiments, at least one Xtetrafluoroborate. In some embodiments, at least one X containsnitrogen. In some embodiments, at least one X is a nitrate. In someembodiments, at least one X is PY₆, wherein Y is a halogen. In someembodiments, at least one X is hexafluorophosphate. In some embodiments,at least one X is NTf₂, and wherein Tf isbis(trifluoromethanesulfonyl)imide.

In some embodiments, Z is one bridge such that the chemical compound hasa general structure (II):

In some embodiments, Z is two bridges such that the chemical compoundhas a general structure (III):

In some embodiments, Z is one bridge such that the chemical compound hasa general structure (IV):

At least one R³ may be a methyl group. At least one R³ may be a C5-C7alkyl group or a C5-C7 substituted alkyl group. At least one R4 may bean aryl group or a substituted aryl group.

In some embodiments, Z is one bridge such that the chemical compound hasa general structure (IVa):

At least one R³ may be a methyl group. At least one R³ may be a C5-C7alkyl group or a C5-C7 substituted alkyl group. At least one R4 may bean aryl group or a substituted aryl group. M may include one or moreguest molecules associated with one or more portions of compound (IVa).

In some embodiments, a method of making a compound may include couplingan at least bifunctional compound with an at least trifunctionalcompound in an alcohol based solvent to form a polycyclic imine compoundincluding at least two cyclic groups, wherein at least one of thebifunctional compound and the at least trifunctional compound comprisetwo or more aldehyde or aldehyde forming moieties, and wherein at leastone of the bifunctional compound and the at least trifunctional compoundcomprise two or more amine or amine forming moieties. The method mayfurther include reducing at least one of the imine moieties of thebridged polycyclic imine compound in an alcohol based solvent with areducing agent to form a bridged polycyclic compound comprising at leasttwo cyclic groups having a general structure (V):

Each R¹ may be independently an alkyl group, a substituted alkyl group,an aryl group, a substituted aryl group, N, a heterocycle group, or asubstituted heterocycle group. Each R² may be independently an alkylgroup, a substituted alkyl group, an aryl group, a substituted arylgroup, a heterocycle group, a substituted heterocycle group, a covalentbond, or an alkene. Each R⁴ may be independently an alkyl group, asubstituted alkyl group, an aryl group, a substituted aryl group, aheterocycle group, a substituted heterocycle group, an ether, an amide,an alcohol, an ester, a sulfonamide, a sulfanilamide, or an alkene. Zmay include at least one bridge. At least one of the bridges may be—R²—N—R⁴═N—R²— or —R²—N═R⁴═N—R²—. Each bridge may independently coupleR¹ to R¹.

In some embodiments, a method may include formation of the polycyclicimine compound followed by reduction of at least one of the iminemoieties of the polycyclic imine compound.

In some embodiments, a method may include formation of the polycyclicimine compound directly followed by reduction of at least one of theimine moieties of the polycyclic imine compound.

In some embodiments, a method may include reducing at least one of theimine moieties of the bridged polycyclic imine compound intetrahydrofuran solvent with a reducing agent comprises using sodiumborohydride as a reducing agent.

In some embodiments, a method may include reducing at least one of theimine moieties of the polycyclic imine compound in an alcohol basedsolvent with a reducing agent comprises using sodium borohydride as areducing agent.

In some embodiments, a method may include reducing at least one of theimine moieties of the bridged polycyclic imine compound in an alcoholbased solvent with a reducing agent comprises using sodium and ammoniaas a reducing agent.

In some embodiments, a method may include alkylating at least four ofthe amines the chemical compound has a general structure (I):

Each R¹ may be independently an alkyl group, a substituted alkyl group,an aryl group, a substituted aryl group, N, N⁺R³, a heterocycle group,or a substituted heterocycle group. Each R² may be independently analkyl group, a substituted alkyl group, an aryl group, a substitutedaryl group, a heterocycle group, a substituted heterocycle group, acovalent bond, or an alkene. Each R³ may be independently an alkylgroup, a substituted alkyl group, an aryl group, a substituted arylgroup, a heterocycle group, a substituted heterocycle group, an alkene,an ether, a PEG, or a PEI. Each R⁴ may be independently an alkyl group,a substituted alkyl group, an aryl group, a substituted aryl group, aheterocycle group, a substituted heterocycle group, an ether, an amide,an alcohol, an ester, a sulfonamide, a sulfanilamide, or an alkene. Zcomprises at least one bridge, wherein at least one of the bridges maybe —R²—N⁺R³ ₂—R⁴—N⁺R³ ₂—R²—, —R²—NR³—R⁴—N⁺R³ ₂—R²—, —R²—NR³—R⁴—NR³—R²—,or —R²—N═R⁴═N—R²—. Each bridge independently couples R¹ to R¹. X mayinclude one or more negatively charged counter ions.

In some embodiments, a method of coating a surface may include applyinga composition to a surface. The composition may include one or morebridged polycyclic compounds. At least one of the bridged polycycliccompounds may include at least two cyclic groups. At least two cyclicgroups may be defined in part by quaternary ammonium moieties. Themethod may include forming an antimicrobial coating over at least aportion of the surface.

In some embodiments, at least one of the bridge polycyclic compounds mayinclude at least four quaternary ammonium moieties which define at leasttwo of the cyclic groups forming the bridged polycyclic compounds.

In some embodiments, at least one of the bridge polycyclic compounds mayinclude at least two phenol moieties which define at least two of thecyclic groups forming the bridged polycyclic compounds.

In some embodiments, at least one of the quaternary ammonium moietiesdefining at least one of the cyclic groups further comprises an alkylgroup, a substituted alkyl group, an aryl group, a heterocycle group, asubstituted heterocycle group, or a substituted aryl group.

In some embodiments, at least one of the quaternary ammonium moietiesdefining at least one of the cyclic groups further comprises an alkylgroup, a substituted alkyl group, an aryl group, or a substituted arylgroup and an alkyl group, a substituted alkyl group, an aryl group, or asubstituted aryl group.

In some embodiments, at least one of the quaternary ammonium moietiesdefining at least one of the cyclic groups further comprises a C6 alkylgroup or a C6 substituted alkyl group and a methyl group or a benzylgroup.

In some embodiments, the bridge polycyclic compound has a generalstructure (I):

In some embodiments, a method of coating a surface may include curingthe composition such that at least a portion of the composition bonds tothe surface.

In some embodiments, the composition may include a polymerizablecompound. The polymerizable compound may include polymerizable amides,esters, olefins, acrylates, methacrylates, urethanes, vinyl esters,epoxy-based materials, styrene, styrene acrylonitrile, sulfones,acetals, carbonates, phenylene ethers, ureas, or phenylene sulfides. Thepolymerizable compound may include 2,2′-bis[4-(3-methacryloxy-2-hydroxypropoxy)-phenyl]-propane, dipentaerythritol pentaacrylate,pentaerythritol dimethacrylate, the condensation product of ethoxylatedbisphenol A and glycidyl methacrylate, the condensation product of 2parts hydroxymethylmethacrylate and 1 part triethylene glycolbis(chloroformate), or polyurethane dimethacrylates. The polymerizablecompound may include hydroxyalkl methacrylates, 2-hydroxyethylmethacrylate, 1,6-hexanediol dimethacrylate, 2-hydroxypropylmethacrylate, glyceryl dimethacrylate, ethyleneglycolmethacrylates,ethyleneglycol methacrylate, diethyleneglycol methacrylate, ortriethyleneglycol methacrylate. The polymerizable compound may includemethacrylic acid, maleic acid p-vinylbenzoic acid,11-methacryloyloxy-1,1-undecanedicarboxylic acid,1,4-dimethacryloyloxyethylpyromellitic acid,6methacryloyloxyethylnaphthalene-1,2,6-tricarboxylic acid,4-methacryloyloxymethyltrimellitic acid and the anhydride thereof,4-methacryloyloxyethyltrimellitic acid and an anhydride thereof,4-(2-hydroxy-3-methacryloyloxy)bultytrimellitic acid and an anhydridethereof, 2,3-bis(3,4-dicarboxybenzoyloxy)propyl methacrylate,methacryloyloxytyrosine, N-methacryloyloxytyrosine,N-methacryloyloxyphenylalanine, methacryloyl-p-aminobenzoic acid, theadduct of 2-hydroxyethyl methacrylate with pyromellitic dianhydride, theadduct of 2-hydroxyethyl methacrylate with maleic anhydride, the adductof 2-hydroxyethyl methacrylate with3,3′,4,4′-benzophenonetetracarboxylic dianhydride, the adduct of2-hydroxyethyl methacrylale with 3,3′,4,4′-biphenyltetracarboxylicdianhydride, the adduct of an aromatic dianhydride with an excess of2-HEMA, the adduct of 2-HEMA with ethylene glycol bistrimellitatedianhydride, the adduct of 3,3′,4,4′-diphenylsulfone tetracarboxylicdianhydide and 2-HEMA, the adduct of pyromellitic dianhydride withglycerol dimethacrylate, 2-methacryloyloxyethyl acidophosphate,2-methacryloyloxypropyl acidophosphate, 4-methacryloyloxybutylacidophosphate, 8-methacryloyloxyoctyl acidophosphate,10-methacryloyloxydecyl acidophosphate,bis(2-methacryloyloxyethyl)acidophosphate, 2-methacryloyloxyethylphenylacidophosphate, 2-sulfoethyl methacrylate, 3-sulfo-2-butyl methaclylate,3-bromro-2-sulfo-2-propyl methacrylate, 3-methoxy-1-sulfo-2-propylmathacrylate, or 1,1-dimethyl-2-sulfoethyl methacrylamide.

In some embodiments, the composition may include an initiator. Theinitiator may include benzil diketones, DL-camphorquinone, peroxides,lauryl peroxide, tributyl hydroperoxide, cumene hydroperoxide,1,1′-azobis(cyclohexanecarbonitrile), or benzoyl peroxide.

In some embodiments, the composition may include an acceleratorcomprising tertiary amines, dimethylaminoethyl methacrylate,diethylaminoethyl methacrylate, aromatic tertiary amines,4-(N,N-dimethyl)aminobenzoate, dimethyl-p-toluidine, anddihydroxyethyl-p-toluidine.

In some embodiments, the composition may include one or more ofultra-violet light absorbers, anti-oxidants, stabilizers, fillers,pigments, opacifiers, gelators, or handling agents.

In some embodiments, the composition may include a filler comprisingamorphous silica, spherical silica, colloidal silica, barium glasses,quartz, ceramic fillers, silicate glass, hydroxyapatite, calciumcarbonate, fluoroaluminosilicate, barium sulfate, quartz, bariumsilicate, strontium silicate, barium borosilicate, bariumboroaluminosilicate, strontium borosilicate, strontiumboroaluminosilicate, glass fibers, lithium silicate, ammoniated calciumphosphate, deammoniated calcium phosphate, alumina, zirconia, tin oxide,polymer powders, polymethyl methacrylate, polystyrene, or polyvinylchloride, titania.

In some embodiments, the composition may include a solvent.

In some embodiments, the composition may include a chelating agent. Thechelating agent may include EDTA.

In some embodiments, the composition may include a boric acid compound.

In some embodiments, at least one X comprises tetrafluoroborate.

In some embodiments, the composition may include sodiumtetrafluoroborate.

In some embodiments, a compound may include a shape with a substantiallycurved surface.

In some embodiments, a coating may be self-cleaning. In someembodiments, a coating may inhibit microbial adhesion.

In some embodiments, a compound may have a minimum inhibitoryconcentration of less than 0.1 mg/mL.

In some embodiments, a composition may have a minimum inhibitoryconcentration of less than 0.05 mg/mL.

In some embodiments, at least one R¹ is N⁺R³. In some embodiments, atleast one R¹ is

In some embodiments, at least one R³ is hydrophilic. In someembodiments, at least one R³ is a polymer. In some embodiments, at leastone R³ is an oxazoline polymer. In some embodiments, at least one R³ ishydrophobic.

In some embodiments, at least one R⁴ may be

In some embodiments, a composition may include at least one metal (M)coordinated to at least a portion of the compound. At least one M mayinclude a cation. At least one M may be positioned inside a spacedefined by R² and R⁴, and wherein at least one M is coordinated to oneor more N⁺R³ ₂'s.

In some embodiments, at least one X may include a halogen ion.

In some embodiments, at least one X may include one or more elementswith antimicrobial activity.

In some embodiments, at least one X may include one or more elementswith antiinflammatory activity

In some embodiments, at least one X may include boron.

In some embodiments, a composition may include one or more metals and/ormetal ions with antimicrobial properties.

In some embodiments, a composition may include one or more metals and/ormetal ions with antiinflammatory properties.

In some embodiments, a composition may include one or more metals and/ormetal ions, and wherein one or more of the metals are light activatedsuch that activating the metal with light increases the antimicrobialactivity of the metal.

In some embodiments, a composition may include one or more metals and/ormetal ions, and wherein at least one metals and/or metal ions is silver.At least one metals and/or metal ions may be zinc, copper, gold, orcesium. At least one metals and/or metal ions may be silver, zinc,copper, gold, calcium, nickel, cobalt, barium, strontium, lead,lanthanum, iron, manganese, cadmium, magnesium, Y, La, Ce, Pr, Nd, Eu,Gd, Tb, Dy, Ho, Er, Tm, Yb, Ce, or alkaline earth metals.

In some embodiments, a method of coating a surface may includepretreating the surface such that the treated surface reacts with thecomposition. In some embodiments, a method of coating a surface mayinclude pretreating the surface such that the treated surface reactswith the composition by coupling an amide precursor electrophile to thesurface. In some embodiments, a method of coating a surface may includepretreating the surface such that the treated surface reacts with thecomposition by coupling maleic anhydride and/or a maleic anhydridederivative to the surface.

In some embodiments, a composition may include a metal oxide coatedbridged polycyclic compound. The metal oxide may include titanium oxide.The metal oxide may include zirconium oxide. The metal oxide may includehafniium oxide. The metal oxide may include boron. The metal oxide mayinclude zinc. The metal oxide may include tantalum. The metal oxide mayinclude titanium oxide, zirconium oxide, hafiium oxide, tungsten oxide,boron, zinc, vanadium, silicon, calcium, bismuth, V, Si, CaBi₂O₄,barium, or tantalum

In some embodiments, a composition may include stabilizers. Thestabilizers may function to increase the solubility of the compound. Thestabilizers may function to increase the solubility of the compound inhydrophobic solvents.

In some embodiments, a composition may include metal oxide coatedbridged polycyclic compound, and the composition may function toincrease the solubility of the compound in hydrophilic solvents.

In some embodiments, a metal oxide coated bridged polycyclic compound islight activated. In some embodiments, a metal oxide coated bridgedpolycyclic compound is light activated such that activating the metaloxide coated bridged polycyclic compound with light increases theantimicrobial activity of the metal oxide coated bridged polycycliccompound. In some embodiments, a metal oxide coated bridged polycycliccompound is ultraviolet light activated such that activating the metaloxide coated bridged polycyclic compound with light increases theantimicrobial activity of the metal oxide coated bridged polycycliccompound.

In some embodiments, a composition may include a matrix.

In some embodiments, a composition may include thermoplastic polymers.

In some embodiments, a composition may include thermosetting polymers.

In some embodiments, a composition may include engineering plastics.

In some embodiments, a composition may include liquid crystal polymers.

In some embodiments, a composition may include aminoacrylic resins.

In some embodiments, a composition may include epoxy resins.

In some embodiments, a composition may include polyurethane resins.

In some embodiments, a composition may include a cross-linking reagent.

In some embodiments, a composition may include a polymerizationcatalyst.

In some embodiments, a composition may include a stabilizer.

In some embodiments, a composition may include a delustering agent.

In some embodiments, a composition may include an optical whiteningagent.

In some embodiments, a composition may include an organic pigment.

In some embodiments, a composition may include an inorganic pigment.

In some embodiments, a composition may include an inorganic filler.

In some embodiments, a composition may include a plasticizer.

In some embodiments, a composition may include a surfactant.

In some embodiments, a composition may include polyvinyl alcohol.

In some embodiments, a composition may include polymethyl methacrylate.

In some embodiments, a composition may include polymethyl-co-polybutylmethacrylate.

In some embodiments, a composition comprises a coalescing solvent.

In some embodiments, a coated surface, may include a chemicalcomposition. At least a portion of the chemical composition may form anantimicrobial coating over at least a portion of a surface. The chemicalcomposition may include one or more bridged polycyclic compounds. Atleast one of the bridged polycyclic compounds may include at least twocyclic groups. At least two cyclic groups may be defined in part byquaternary ammonium moieties.

In some embodiments, a compound and/or a coating composition may have aminimum inhibitory concentration of greater than 900 μM (e.g., 900μM-1500 μM, 900 μM-2000 μM, 1500 μM-2500 μM, etc.). In some embodiments,a compound and/or a coating composition may have a minimum inhibitoryconcentration of less than 10.0 mg/mL less than 5.0 mg/mL, less than 1.0mg/mL, less than 0.1 mg/mL, or less than 0.05 mg/mL. In suchcompositions, antimicrobial properties may not be the primary functionof a coating composition. For example, self-cleaning properties may bethe primary focus of the coating composition.

In some embodiments, at least some of the herein described compoundsincludes a metal oxide coating or shell. The metal oxide may includetitanium oxide, zirconium oxide, haffiium oxide, boron, zinc, vanadium,silicon, calcium, bismuth, barium or tantalum. Metal oxide shells mayinclude metals which are light activated such that activation with lightincreases the antimicrobial activity of the compound and metal oxide inparticular. In some embodiments, a metal oxide shell may includestabilizers. Stabilizers may function to increase the solubility of acompound in hydrophobic and/or hydrophilic solvents.

In some embodiments, a method of coating a building substrate, mayinclude applying a composition to a surface of a building substrate. Thecomposition may include one or more bridged polycyclic compounds. Atleast one of the bridged polycyclic compounds may include at least twocyclic groups. At least two cyclic groups may be defined in part byquaternary ammonium moieties. The method may include forming anantimicrobial coating over at least a portion of the surface.

The building substrate may include at least a portion of an interiorand/or exterior wall, one or more structural supports of a building, orat least a portion of a roof and/or ceiling.

The method may include using the composition as a primer for thesurface.

The method may include using the composition as a sealant for thesurface.

The composition may include a pigment and the method further includingusing the composition as a paint for the surface.

The composition may include a chelating agent. The chelating agent mayinclude EDTA.

The composition may include a boric acid compound.

At least one X of the compound may include tetrafluoroborate.

In some embodiments, a coating composition may include sodiumtetrafluoroborate.

In some embodiments, a coating composition may include potassiumtetrafluoroborate.

In some embodiments, a building substrate may be coated with a coatingThe coating may include a chemical composition at least a portion ofwhich forms an antimicrobial coating over at least a portion of asurface of the building substrate. The chemical composition may includeone or more bridged polycyclic compounds. At least one of the bridgedpolycyclic compounds may include at least two cyclic groups. At leasttwo cyclic groups may be defined in part by quaternary ammoniummoieties.

In some embodiments, a method of coating a marine substrate, may includeapplying a composition to a surface of a marine substrate. Thecomposition may include one or more bridged polycyclic compounds. Atleast one of the bridged polycyclic compounds may include at least twocyclic groups. At least two cyclic groups may be defined in part byquaternary ammonium moieties. The method may include forming anantimicrobial coating over at least a portion of the surface.

The method may include inhibiting the growth of bacteria on the surface.

The marine substrate may include at least a portion of a boat, at leasta portion of an outer hull of a boat, at least a portion of a pier, atleast a portion of a boat dock, at least a portion of an outer hull of asubmersible vessel, at least a portion of a surf board, or at least aportion of a offshore oil and/or gas rig.

In some embodiments, a marine substrate may be coated with a coating Thecoating may include a chemical composition at least a portion of whichforms an antimicrobial coating over at least a portion of a surface ofthe marine substrate. The chemical composition may include one or morebridged polycyclic compounds. At least one of the bridged polycycliccompounds may include at least two cyclic groups. At least two cyclicgroups may be defined in part by quaternary ammonium moieties.

In some embodiments, a method of inhibiting growth of mollusks on amarine substrate, may include applying a composition to a surface of amarine substrate. The composition may include one or more bridgedpolycyclic compounds. At least one of the bridged polycyclic compoundsmay include at least two cyclic groups. At least two cyclic groups maybe defined in part by quaternary ammonium moieties. The method mayinclude forming an antimicrobial coating over at least a portion of thesurface. The method may include inhibiting growth of mollusks on themarine substrate to which the composition has been applied.

In some embodiments, a method of coating an oral surface, may includeapplying a composition to a surface of an oral surface. The compositionmay include one or more bridged polycyclic compounds. At least one ofthe bridged polycyclic compounds may include at least two cyclic groups.At least two cyclic groups may be defined in part by quaternary ammoniummoieties. The method may include forming an antimicrobial coating overat least a portion of the surface.

The oral surface may include at least a portion of a tooth surface, atleast a portion of a gum, at least a portion of soft tissue, or at leasta portion of a dental fixture. A dental fixture may include a filling,at least a portion of a bridge, or at least a portion of a denture.

The composition may be in the form of a gel.

In some embodiments, a composition may include a coalescing solvent.

The method may include using the composition as a bonding agent.

The method may include using the composition as a resin cement.

The method may include using the composition as a sealant.

The method may include using the composition as a varnish.

The method may include using the composition as a resin.

In some embodiments, an oral surface may be coated with a coating Thecoating may include a chemical composition at least a portion of whichforms an antimicrobial coating over at least a portion of the oralsurface. The chemical composition may include one or more bridgedpolycyclic compounds. At least one of the bridged polycyclic compoundsmay include at least two cyclic groups. At least two cyclic groups maybe defined in part by quaternary ammonium moieties.

In some embodiments, a method of coating a medical device, may includeapplying a composition to a surface of a medical device. The compositionmay include one or more bridged polycyclic compounds. At least one ofthe bridged polycyclic compounds may include at least two cyclic groups.At least two cyclic groups may be defined in part by quaternary ammoniummoieties. The method may include forming an antimicrobial coating overat least a portion of the surface.

In some embodiments, a medical device may include at least a portion ofa stent, at least a portion of a catheter, at least a portion of acannulae, at least a portion of a contact lenses, or at least a portionof a feeding tube.

In some embodiments, a composition may be included as part of anapplication kit for coating at least a portion of the medical device.

In some embodiments, a medical device may be coated with a coating Thecoating may include a chemical composition at least a portion of whichforms an antimicrobial coating over at least a portion of the medicaldevice. The chemical composition may include one or more bridgedpolycyclic compounds. At least one of the bridged polycyclic compoundsmay include at least two cyclic groups. At least two cyclic groups maybe defined in part by quaternary ammonium moieties.

In some embodiments, a method of coating a personal care device, mayinclude applying a composition to a surface of a personal care device.The composition may include one or more bridged polycyclic compounds. Atleast one of the bridged polycyclic compounds may include at least twocyclic groups. At least two cyclic groups may be defined in part byquaternary ammonium moieties. The method may include forming anantimicrobial coating over at least a portion of the surface.

In some embodiments, a composition may be included as part of anapplication kit for coating at least a portion of the personal caredevice.

In some embodiments, a personal care device may include a foot bath, apedicure bath system, or one or more pedicure instruments.

In some embodiments, a personal care device may be coated with a coatingThe coating may include a chemical composition at least a portion ofwhich forms an antimicrobial coating over at least a portion of thepersonal care device. The chemical composition may include one or morebridged polycyclic compounds. At least one of the bridged polycycliccompounds may include at least two cyclic groups. At least two cyclicgroups may be defined in part by quaternary ammonium moieties.

BRIEF DESCRIPTION OF THE DRAWINGS

Advantages of the present invention may become apparent to those skilledin the art with the benefit of the following detailed description of thepreferred embodiments and upon reference to the accompanying drawings inwhich:

FIG. 1 depicts a graphical representation of time kill assay tests for abridged polycyclic compound tested against Staphylococcus aureaus.

FIG. 2 depicts a graphical representation of time kill assay tests for abridged polycyclic compound tested against Escherichia coli.

FIG. 3 depicts a graphical representation of time kill assay tests for abridged polycyclic compound tested against Escherichia coli.

FIG. 4 depicts a graphical representation of time kill assay tests for abridged polycyclic compound tested against Aspergillus niger.

While the invention is susceptible to various modifications andalternative forms, specific embodiments thereof are shown by way ofexample in the drawings and may herein be described in detail. Thedrawings may not be to scale. It should be understood, however, that thedrawings and detailed description thereto are not intended to limit theinvention to the particular form disclosed, but on the contrary, theintention is to cover all modifications, equivalents and alternativesfalling within the spirit and scope of the present invention as definedby the appended claims.

DETAILED DESCRIPTION

It is to be understood the present invention is not limited toparticular devices or biological systems, which may, of course, vary. Itis also to be understood that the terminology used herein is for thepurpose of describing particular embodiments only, and is not intendedto be limiting. As used in this specification and the appended claims,the singular forms “a”, “an”, and “the” include singular and pluralreferents unless the content clearly dictates otherwise. Thus, forexample, reference to “a linker” includes one or more linkers.

DEFINITIONS

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art.

The term “accelerator” as used herein generally refers to a substancethat speeds a chemical reaction.

The term “acyl” as used herein generally refers to a carbonylsubstituent, —C(O)R, where R is alkyl or substituted alkyl, aryl, orsubstituted aryl, which may be called an alkimoyl substituent when R isalkyl.

The term “adhesive” as used herein generally refers to a substance(e.g., glue, starch, paste, or mucilage) that bonds two materialstogether by adhering to the surface of each.

The term “aldehyde” as used herein generally refers to any of a class oforganic compounds containing the group —CHO

The term “aldehyde forming moiety” as used herein generally refers toany of a class of organic compounds which form an aldehyde in solutionor react in an equivalent manner to an aldehyde such that an at leastsimilar chemical product is aclieved as would have been achieved with analdehyde.

The terms “alkenyl” and “alkene” as used herein generally refer to anystructure or moiety having the unsaturation C═C. As used herein, theterm “alkynyl” generally refers to any structure or moiety having theunsaturation C≡C.

The term “alkoxy” generally refers to an —OR group, where R is an alkyl,substituted lower alkyl, aryl, substituted aryl. Alkoxy groups include,for example, methoxy, ethoxy, phenoxy, substituted phenoxy, benzyloxy,phenethyloxy, t-butoxy, and others.

The term “alkyl” as used herein generally refers to a chemicalsubstituent containing the monovalent group C_(n)H_(2n), where n is aninteger greater than zero. Alkyl includes a branched or unbranchedmonovalent hydrocarbon radical. An “n-mC” alkyl or “(nC-mC)alkyl” refersto all alkyl groups containing from n to m carbon atoms. For example, a1 -4C alkyl refers to a methyl, ethyl, propyl, or butyl group. Allpossible isomers of an indicated alkyl are also included. Thus, propylincludes isopropyl, butyl includes n-butyl, isobutyl and t-butyl, and soon. The term alkyl may include substituted alkyls.

The term “alkyl-aryl” as used herein generally refers to a chemicalsubstituent containing an alkyl group coupled to an aryl group or asubstituted aryl group.

The terms “amino” or “amine” as used herein generally refer to a group—NRR′, where R and R′ may independently include, but are not limited to,hydrogen, alkyl, substituted alkyl, aryl, substituted aryl or acyl.

The terms “amine forming moiety” as used herein generally refers to anyof a class of organic compounds which form an amine in solution or reactin an equivalent manner to an anmine such that an at least similarchemical product is achieved as would have been achieved with an amine.

The terms “amphiphile” or “amphiphilic” as used herein generally referto a molecule or species which exhibits both hydrophilic and lipophiliccharacter. In general, an amphiphile contains a lipophilic moiety and ahydrophilic moiety. The terms “lipophilic” and “hydrophobic” areinterchangeable as used herein. An amphiphile may form a Langmuir film.

Non-limiting examples of hydrophobic groups or moieties include loweralkyl groups, alkyl groups having 6, 7, 8, 9, 10, 11, 12, or more carbonatoms, including alkyl groups with 14-30, or 30 or more carbon atoms,substituted alkyl groups, alkenyl groups, alkynyl groups, aryl groups,substituted aryl groups, saturated or unsaturated cyclic hydrocarbons,heteroaryl, heteroarylalkyl, heterocyclic, and corresponding substitutedgroups. A hydrophobic group may contain some hydrophilic groups orsubstituents insofar as the hydrophobic character of the group is notoutweighed. In further variations, a hydrophobic group may includesubstituted silicon atoms, and may include fluorine atoms. Thehydrophobic moieties may be linear, branched, or cyclic.

Non-limiting examples of hydrophilic groups or moieties includehydroxyl, methoxy, phenyl, carboxylic acids and salts thereof, methyl,ethyl, and vinyl esters of carboxylic acids, amides, amino, cyano,isocyano, nitrile, ammonium salts, sulfonium salts, phosphonium salts,mono- and di-alkyl substituted amino groups, polypropyleneglycols,polyethylene glycols, epoxy groups, acrylates, sulfonamides, nitro,—OP(O)(OCH₂CH₂N⁺RRR)O⁻, guanidinium, aminate, acrylamide, pyridinium,piperidine, and combinations thereof, wherein each R is independentlyselected from H or alkyl. Further examples include polymethylene chainssubstituted with alcohol, carboxylate, acrylate, or methacrylate.Hydrophilic moieties may also include alkyl chains having internal aminoor substituted amino groups, for example, internal —NH—, —NC(O)R—, or—NC(O)CH═CH₂— groups, wherein R is H or alkyl. Hydrophilic moieties mayalso include polycaprolactones, polycaprolactone diols, poly(aceticacid)s, poly(vinyl acetates)s, poly(2-vinyl pyridine)s, celluloseesters, cellulose hydroxylethers, poly(L-lysine hydrobromide)s,poly(itaconic acid)s, poly(maleic acid)s, poly(styrenesulfonic acid)s,poly(aniline)s, or poly(vinyl phosphonic acid)s. A hydrophilic group maycontain some hydrophobic groups or substituents insofar as thehydrophilic character of the group is not outweighed.

The term “aryl” as used herein generally refers to a chemicalsubstituent containing an aromatic group (e.g., phenyl). An aromaticgroup may be a single aromatic ring or multiple aromatic rings which arefused together, coupled covalently, or coupled to a common group such asa methylene, ethylene, or carbonyl, and includes polynuclear ringstructures. An aromatic ring or rings may include, but is not limitedto, substituted or unsubstituted phenyl, naphthyl, biphenyl,diphenylmethyl, and benzophenone groups. The term “aryl” includessubstituted aryls The term “antiinflammatory” as used herein generallyrefers to a substance acting to reduce certain signs of inflammation(e.g., swelling, tenderness, fever, and pain).

The term “antimicrobial” as used herein generally refers to a substancecapable of destroying or inhibiting the growth of microbes, prevents thedevelopment of microbes, and/or inhibits the pathogenic action ofmicrobes as well as viruses, fungi, and bacteria.

The term “bridged polycyclic compound” as used herein generally refersto a compound that is composed of two or more cyclic systems that sharetwo or more atoms. A cyclic system is formed from a group of atoms whichtogether form a continuous loop. A bridged polycyclic compound mayinclude a bridging atom or group of atoms that connects two or morenon-adjacent positions of the same ring. An example of a bridgedbicyclic system (i.e., a compound composed of two cyclic systems) withtwo atoms (atoms “A”) common to both cyclic systems is depicted below.One of the linking groups “L” represents a bridging atom or group ofatoms.

The term “building substrate” as used herein generally refers to anatural or synthetic material used in the construction of a residentialor commercial structure.

The term “cavitand” as used herein generally refers to a natural orsynthetic molecular compound with enforced cavities large enough tocomplex complementary compounds or ions. More specifically, a cavitandmay be generally defined as a three-dimensional compound that maintainsa substantially rigid structure and binds a variety of molecules in thecavities produced by the structure of the three-dimensional compound.

The term “chelating agent or complexing agent” as used herein generallyrefers to any of various compounds that combine with metals to formchelates.

The term “coalescing agents or solvents” as used herein generally refersto any of various compounds that are used in coatings to promote filmformation (e.g., in architectural and industrial latex coating).

The term “coating” as used herein generally includes coatings thatcompletely cover a surface, or portion thereof, as well as coatings thatmay only partially cover a surface, such as those coatings that afterdrying leave gaps in coverage on a surface. The later category ofcoatings may include, but is not limited to a network of covered anduncovered portions (e.g., non-continuous covered regions of thesurface). When the coatings described herein are described as beingapplied to a surface, it is understood that the coatings need not beapplied to, or that they cover the entire surface. For instance, thecoatings will be considered as being applied to a surface even if theyare only applied to modify a portion of the surface. The coating may beapplied to a surface or impregnated within the material used toconstruct an item or a portion of an item.

The terms “coupling” and “coupled” with respect to molecular moieties orspecies, atoms, synthons, cyclic compounds, and nanoparticles refers totheir attachment or association with other molecular moieties orspecies, atoms, synthons, cyclic compounds, and nanoparticles. Theattachment or association may be specific or non-specific, reversible ornon-reversible, the result of chemical reaction, or complexation orcharge transfer. The bonds formed by a coupling reaction are oftencovalent bonds, or polar-covalent bonds, or mixed ionic-covalent bonds,and may sometimes be Coulombic forces, ionic or electrostatic forces orinteractions.

The terms “crystalline” or “substantially crystalline”, when used withrespect to nanostructures, refer to the fact that the nanostructurestypically exhibit long-range ordering across one or more dimensions ofthe structure. It will be understood by one of skill in the art that theterm “long range ordering” will depend on the absolute size of thespecific nanostructures, as ordering for a single crystal typically doesnot extend beyond the boundaries of the crystal. In this case,“long-range ordering” will mean substantial order across at least themajority of the dimension of the nanostructure. In some instances, ananostructure may bear an oxide or other coating, or may be comprised ofa core and at least one shell. In such instances it will be appreciatedthat the oxide, shell(s), or other coating need not exhibit suchordering (e.g., it may be amorphous, polycrystalline, or otherwise). Insuch instances, the phrase “crystalline,” “substantially crystalline,”“substantially monocrystalline,” or “monocrystalline” refers to thecentral core of the nanostructure (excluding the coating layers orshells). The terms “crystalline” or “substantially crystalline” as usedherein are intended to also encompass structures comprising variousdefects, stacking faults, atomic substitutions, etc., as long as thestructure exhibits substantial long range ordering (e.g., order over atleast about 80% of the length of at least one axis of the nanostructureor its core). It may be appreciated that the interface between a coreand the outside of a nanostructure or between a core and an adjacentshell or between a shell and a second adjacent shell may containnon-crystalline regions and may even be amorphous. This does not preventthe nanostructure from being crystalline or substantially crystalline asdefined herein.

The term “cyclic” as used herein generally refers to compounds havingwherein at least some of the atoms are arranged in a ring orclosed-chain structure.

The term “dental compositions” as used herein generally refers to anysubstances typically associated with any type of dental work and/or inrelated fields and includes, but is not limited to, dental primers,adhesives, surface sealants, liners, luting cements, varnishes,impression materials, equipment and impression systems, and compositerestoratives.

The term “dental fixture” as used herein generally refers to an at leastpartially synthetic material configured to positioned in and/or coupledto at least a portion of an oral cavity. For example a dental fixturemay include, but is not limited to, a filling, a bridge, a false tooth,a cap, or denture.

The term “effective concentration” or “effective amount” as used hereingenerally refers to a sufficient amount of the antimicrobial agent isadded to decrease, prevent or inhibit the growth of microbial organisms.The amount will vary for each compound and upon known factors related tothe item or use to which the antimicrobial agent is applied.

The term “film” as used herein generally refers to a thin sheet ofmaterial (e.g., plastic) used to at least partially cover at least aportion of a surface. The material may be transparent, translucent, oropaque. The film may be a solid continuous sheet or the film may containperforations (e.g., a web like material).

The terms “functionalized” or “functional group” as used hereingenerally refers to the presence of a reactive chemical moiety orfunctionality. A functional group may include, but is not limited to,chemical groups, biochemical groups, organic groups, inorganic groups,organometallic groups, aryl groups, heteroaryl groups, cyclichydrocarbon groups, amino (—NH₂), hydroxyl (—OH), cyano (—C≡N), nitro(NO₂), carboxyl (—COOH), formyl (—CHO), keto (—CH₂C(O)CH₂—), ether(—CH₂—O—CH₂—), thioether (—CH₂—S—CH₂—), alkenyl (—C═C—), alkynyl,(—C≡C—), epoxy

metalloids (functionality containing Si and/or B) and halo (F, Cl, Br,and I) groups. In some embodiments, the functional group is an organicgroup.

The term “gram-negative bacteria” or “gram-negative bacterium” as usedherein generally refers to bacteria which have been classified by theGram stain as having a red stain. Gram-negative bacteria have thinwalled cell membranes consisting of a single layer of peptidoglycan andan outer layer of lipopolysacchacide, lipoprotein, and phospholipid.Exemplary organisms include, but are not limited to, Enterobacteriaceaconsisting of Escherichia, Shigella, Edwardsiella, Salmonella,Citrobacter, Klebsiella, Enterobacter, Hafnia, Serratia, Proteus,Morganella, Providencia, Yersinia, Erwinia, Buttlauxella, Cedecea,Ewingella, Kluyvera, Tatumella and Rahnella. Other exemplarygram-negative organisms not in the family Enterobacteriacea include, butare not limited to, Pseudomonas aeruginosa, Stenotrophomonasmaltophilia, Burkholderia, Cepacia, Gardenerella, Vaginalis, andAcinetobacter species.

The term “gram-positive bacteria” or “gram-positive bacterium” as usedherein refers to bacteria, which have been classified using the Gramstain as having a blue stain. Gram-positive bacteria have a thick cellmembrane consisting of multiple layers of peptidoglycan and an outsidelayer of teichoic acid. Exemplary organisms include, but are not limitedto, Staphylococcus aureus, coagulase-negative staphylococci,streptococci, enterococci, corynebacteria, and Bacillus species.

The term “heteroaryl” generally refers to a completely unsaturatedheterocycle.

The term “heterocycle” as used herein generally refers to a closed-ringstructure, in which one or more of the atoms in the ring is an elementother than carbon. Heterocycle may include aromatic compounds ornon-aromatic compounds. Heterocycles may include rings such asthiophene, pyridine, isoxazole, phthalimide, pyrazole, indole, furan, orbenzo-fused analogues of these rings. Examples of heterocycles includetetrahydrofuran, morpholine, piperidine, pyrrolidine, and others. Insome embodiments, “heterocycle” is intended to mean a stable 5- to7-membered monocyclic or bicyclic or 7- to 10-membered bicyclicheterocyclic ring which is either saturated or unsaturated, and whichconsists of carbon atoms and from 1 to 4 heteroatoms (e.g., N, O, and S)and wherein the nitrogen and sulfur heteroatoms may optionally beoxidized, and the nitrogen may optionally be quatemized, and includingany bicyclic group in which any of the above-defined heterocyclic ringsis fused to a benzene ring. In some embodiments, heterocycles mayinclude cyclic rings including boron atoms. The heterocyclic ring may beattached to its pendant group at any heteroatom or carbon atom whichresults in a stable structure. The heterocyclic rings described hereinmay be substituted on carbon or on a nitrogen atom if the resultingcompound is stable. Examples of such heterocycles include, but are notlimited to, 1H-indazole, 2-pyrrolidonyl, 2H16H-1,5,2-dithiazinyl,2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4a H-carbazole, 4H-quinolizinyl,6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzofuranyl,benzothiophenyl, carbazole, chromanyl, chromenyl, cinnolinyl,decahydroquinolinyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl,imidazolyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl,isochromanyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl),isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl,octahydroisoquinolinyl, oxazolidinyl, oxazolyl, phenanthridinyl,phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl,pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl,quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl,tetrahydroquinolinyl, tetrazolyl, thianthrenyl, thiazolyl, thienyl,thiophenyl, triazinyl, xanthenyl. Also included are fused ring and spirocompounds containing, for example, the above heterocycles.

The term “initiator” as used herein generally refers to a substance thatinitiates a chemical reaction.

The term “ion” as used herein generally refers to an atom(s), radical,or molecule(s) that has lost or gained one or more electrons and hasthus acquired an electric charge.

The terms “marine” or “marine substrate” as used herein generally referto any aqueous environment including sea and freshwater either in theopen environment such as the ocean, a lake or river, or any otherextensively submerged surface such as the lining of a pipe, a pier orthe inner surface of a fish tank, a water intake and discharge systemsfor reservoirs, for example.

The term “matrix” generally refers to a material, often a polymericmaterial and/or a prepolymeric material, into which a second material(e.g., a nanostructure) is embedded, surrounded, or otherwiseassociated. A matrix is typically composed of one or more monomers, butmay include other matrix components/constituents. Often the matrixconstituents include one or more “addressable” components orcomplementary binding pairs, that optionally promote assembly and/orcross-linkage of the matrix.

The term “medical device” as used herein generally refers to a deviceused which pertains to treating or determining the state of one'shealth. Medical devices are any article that contacts patients or areused in health care, and may be for use either internally or externally.

The term “microbe” as used herein generally refers to a minute lifeform; a microorganism. In some embodiments, a microbe may include abacterium that causes disease.

The term “mollusks” as used herein generally refers to any of numerousinvertebrate animals of the phylum Mollusca, usually living in water andoften having a hard outer shell (e.g., barnacles, clams, oysters). Theyhave a muscular foot, a well-developed circulatory and nervous system,and often complex eyes. Mollusks may include gastropods (snails andshellfish), slugs, octopuses, squids, and the extinct ammonites.

The term “monocrystalline” when used with respect to a nanostructureindicates that the nanostructure is substantially crystalline andcomprises substantially a single crystal. When used with respect to ananostructure heterostructure comprising a core and one or more shells,“monocrystalline” indicates that the core is substantially crystallineand comprises substantially a single crystal.

The terms “monofunctional”, “bifunctional”, “trifunctional”, and“multifunctional” generally refers to a number of attachment sites aparticular compound, molecule, atom, etc. may include (monofunctionalhaving one site, bifunctional having two sites, trifunctional havingthree sites, and multifunctional having more than one site).

The term “nanocrystal” as used herein generally refers to ananostructure that is substantially monocrystalline. A nanocrystal thushas at least one region or characteristic dimension with a dimension ofless than about 500 nm, e.g., less than about 200 nm, less than about100 nm, less than about 50 nm, or even less than about 20 nm. The regionor characteristic dimension may be along the smallest axis of thestructure. Examples of such structures include nanowires, nanorods,nanotubes, branched nanowires, nanotetrapods, nanotripods, nanobipods,nanocrystals, nanodots, quantum dots, nanoparticles, nanoribbons, etc.Nanostructures may be substantially homogeneous in material properties,or in certain embodiments may be heterogeneous (e.g., heterostructures).Optionally, a nanocrystal may comprise one or more surface ligands(e.g., surfactants). The nanocrystal is optionally substantially singlecrystal in structure (a “single crystal nanostructure” or a“monocrystalline nanostructure”). Nanostructures may be fabricated fromessentially any convenient material or material, the nanostructure maybe prepared from an inorganic material, e.g., an inorganic conductive orsemiconductive material. A conductive or semi-conductive nanostructureoften displays 1-dimensional quantum confinement, e.g., an electron mayoften travel along only one dimension of the structure. Nanocrystals maybe substantially homogeneous in material properties, or in certainembodiments may be heterogeneous (e.g., heterostructures). The term“nanocrystal” is intended to encompass substantially monocrystallinenanostructures comprising various defects, stacking faults, atomicsubstitutions, etc., as well as substantially monocrystallinenanostructures without such defects, faults, or substitutions. In thecase of nanocrystal heterostructures comprising a core and one or moreshells, the core of the nanocrystal is typically substantiallymonocrystalline, but the shell(s) need not be. The nanocrystals may befabricated from essentially any convenient material or materials.

The terms “nanostructure” or “nanoparticle” are used herein to generallyrefer to a structure having at least one region or characteristicdimension with a dimension of less than about 500 nm, e.g., less thanabout 200 nm, less than about 100 nm, less than about 50 nm, or evenless than about 20 nm. The region or characteristic dimension may bealong the smallest axis of the structure. Examples of such structuresinclude nanowires, nanorods, nanotubes, branched nanocrystals,nanotetrapods, tripods, bipods, nanocrystals, nanodots, quantum dots,nanoparticles, branched tetrapods (e.g., inorganic dendrimers), etc.Nanostructures may be substantially homogeneous in material properties,or in certain embodiments may be heterogeneous (e.g., heterostructures).Nanostructures may be, e.g., substantially crystalline, substantiallymonocrystalline, polycrystalline, amorphous, or a combination thereof.In one aspect, each of the three dimensions of the nanostructure has adimension of less than about 500 nm, e.g., less than about 200 nm, lessthan about 100 nm, less than about 50 nm, or even less than about 20 nm.Nanostructures may comprise one or more surface ligands (e.g.,surfactants).

The terms “oligomeric” and “polymeric” are used interchangeably hereinto generally refer to multimeric structures having more than onecomponent monomer or subunit.

The term “oral surface” as used herein generally refers to a portion ofthe mouth and/or something positioned in and/or coupled to a portion ofthe mouth. For example an oral surface may include, but is not limitedto, at least a portion of a tooth, at least a portion of the gum, atleast a portion of the tongue, at least a portion of a dental fixture(e.g., a filling, a bridge, a cap a false tooth).

The term “pharmaceutically acceptable salts” includes salts preparedfrom by reacting pharmaceutically acceptable non-toxic bases or acids,including inorganic or organic bases, with inorganic or organic acids.Pharmaceutically acceptable salts may include salts derived frominorganic bases include aluminum, ammonium, calcium, copper, ferric,ferrous, lithium, magnesium, manganic salts, manganous, potassium,sodium, zinc, etc. Examples include the ammonium, calcium, magnesium,potassium, and sodium salts. Salts derived from pharmaceuticallyacceptable organic non-toxic bases include salts of primary, secondary,and tertiary amines, substituted amines including naturally occurringsubstituted amines, cyclic amines, and basic ion exchange resins, suchas arginine, betaine, caffeine, choline, N,N′-dibenzylethylenediamine,diethylamine, 2-dibenzylethylenediamine, 2-diethylaminoethanol,2-dimethylaminoethanol, ethanolamine, ethylenediamine,N-ethyl-morpholine, N-ethylpiperidine, glucamine, glucosamine,histidine, hydrabamine, isopropylamine, lysine, methylglucamine,morpholine, piperazine, piperidine, polyamine resins, procaine, purines,theobromine, triethylamine, trimethylamine, tripropylamine,tromethamine, etc.

The term “personal care” item and/or associated facility as used hereingenerally refers to a device or system used in or typically associatedwith a salon (e.g., hair and/or nail) or a day spa, including footbaths,or any device which comes into contact with multiple persons and/orcontains such devices, thereby potentially passing along harmfulbacteria.

The term “polycyclic,” as used herein, generally refers to a chemicalcompound having two or more atomic rings in a molecule. Steroids arepolycyclic compounds. The term “polymerizable compound,” as used herein,generally refers to a chemical compound, substituent or moiety capableof undergoing a self-polymerization and/or co-polymerization reaction(e.g., vinyl derivatives, butadienes, trienes, tetraenes, dialkenes,acetylenes, diacetylenes, styrene derivatives).

The term “primer,” as used herein, generally refers to an undercoat ofpaint or size applied to prepare a surface (e.g., for painting).

The term “quaternary ammonium moiety,” as used herein, generally refersto a tetravalent charged nitrogen (e.g., N⁺R³ ₄).

The terms “R^(n)” in a chemical formula refer to a hydrogen or afunctional group, each independently selected, unless stated otherwise.In some embodiments the functional group may be an organic group. Insome embodiments the functional group may be an alkyl group. In someembodiment, the functional group may be a hydrophobic or hydrophilicgroup.

The terms “reducing,” “inhibiting” and “ameliorating,” as used herein,when used in the context of modulating a pathological or disease state,generally refers to the prevention and/or reduction of at least aportion of the negative consequences of the disease state. When used inthe context of an adverse side effect associated with the administrationof a drug to a subject, the term(s) generally refer to a net reductionin the severity or seriousness of said adverse side effects.

The term “sealant,” as used herein, generally refers to any of variousliquids, paints, chemicals, or soft substances that may be applied to asurface or circulated through a system of pipes or the like, drying toform a hard, substantially watertight coating. When used in the contextof dentistry sealant generally refers to any of several transparentsynthetic resins applied to the chewing surfaces of an oral cavity as apreventive measure against tooth decay in the occlusal pits andfissures.

The term “self-cleaning” (e.g., surfaces) as used herein generallyrefers to a surface which inhibits adhesion of matter to the surface.Self-cleaning generally refers to the mechanisms of adhesion between twosurfaces which are in contact. These systems generally attempt to reducetheir free surface energy. If the free surface energies between twocomponents are intrinsically very low, it may generally be assumed thatthere will be weak adhesion between these two components. The importantfactor here is the relative reduction in free surface energy. Inpairings where one surface energy is high and one surface energy is lowthe crucial factor is very often the opportunity for interactiveeffects, for example, when water is applied to a hydrophobic surface itis impossible to bring about any noticeable reduction in surface energy.This is evident in that the wetting is poor. The water applied formsdroplets with a very high contact angle. Perfluorinated hydrocarbons(e.g., polytetrafluoroethylene) have very low surface energy. There arehardly any components which adhere to surfaces of this type, andcomponents deposited on surfaces of this type are in turn very easy toremove. The term self-cleaning as used herein also generally refers to achemical transformation of a contaminant that comes into contact withthe surface such that it is broken down by oxidative decomposition(e.g., photooxidation by a metal oxide such as photocatalytic oxidationof phenol or E. Coli inactivation due to photooxidation by TiO₂).

The term “substituted alkyl” as used herein generally refers to an alkylgroup with an additional group or groups attached to any carbon of thealkyl group. Substituent groups may include one or more functionalgroups such as alkyl, lower alkyl, aryl, acyl, halogen, alkylhalo,hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy, aryloxy,aryloxyalkyl, mercapto, both saturated and unsaturated cyclichydrocarbons, heterocycles, and other organic groups.

The term “substituted alkyl-aryl” as used herein generally refers to analkyl-aryl group with an additional group or groups attached to anycarbon of the alkyl-aryl group. Additional groups may include one ormore functional groups such as lower alkyl, aryl, acyl, halogen,alkylhalo, hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy,aryloxy, aryloxyalkyl, thioether, heterocycles, both saturated andunsaturated cyclic hydrocarbons which are fused to the aromatic ring(s),coupled covalently or coupled to a common group such as a methylene orethylene group, or a carbonyl coupling group such as in cyclohexylphenyl ketone, and others.

The term “substituted aryl” as used herein generally refers to an arylgroup with an additional group or groups attached to any carbon of thearyl group. Additional groups may include one or more functional groupssuch as lower alkyl, aryl, acyl, halogen, alkylhalo, hydroxy, amino,alkoxy, alkylamino, acylamino, acyloxy, aryloxy, aryloxyalkyl,thioether, heterocycles, both saturated and unsaturated cyclichydrocarbons which are fused to the aromatic ring(s), coupled covalentlyor coupled to a common group such as a methylene or ethylene group, or acarbonyl coupling group such as in cyclohexyl phenyl ketone, and others.

The term “substituted heterocycle” as used herein generally refers to aheterocyclic group with an additional group or groups attached to anyelement of the heterocyclic group. Additional groups may include one ormore functional groups such as lower alkyl, aryl, acyl, halogen,alkylhalos, hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy,aryloxy, aryloxyalkyl, thioether, heterocycles, both saturated andunsaturated cyclic hydrocarbons which are fused to the heterocyclicring(s), coupled covalently or coupled to a common group such as amethylene or ethylene group, or a carbonyl coupling group such as incyclohexyl phenyl ketone, and others.

The term “substrate” as used herein generally refers to a body or baselayer or material (e.g., onto which other layers are deposited).

The term “thioether” as used herein generally refers to the generalstructure R—S—R′ in which R and R′ are the same or different and may bealkyl, aryl or heterocyclic groups. The group —SH may also be referredto as “sulfhydryl” or “thiol” or “mercapto.”

Bridged Polycyclic Antimicrobials

New antimicrobials are required to combat the new antimicrobialresistant microbes. New antimicrobials may be effective verses microbeswhich are currently resistant to currently known antimicrobials. Newantimicrobials may resist leaching off into the environment beyond apredetermined amount to inhibit polluting the environment unnecessarily(which may concurrently increase the occurrence of antimicrobialresistant microbes from overexposure of antimicrobials).

One strategy for combating antimicrobial resistant organisms is bymodifying known antimicrobials to increase their effectiveness. In someembodiments, quaternary ammonium compounds may be modified to increasetheir effectiveness. It is typically thought that quaternary ammoniumcompounds denature the proteins of the bacterial or fungal cell, affectthe metabolic reactions of the cell and allow vital substances to leakout of the cell, finally causing death. In addition, quaternary ammoniumcompounds are not known to be toxic towards higher forms of life (e.g.,humans).

One of the main considerations in examining the mode of action is thecharacterization of quaternary ammonium compounds as cationicsurfactants. This class of chemical reduces the surface tension atinterfaces, and is attracted to negatively charged surfaces, includingmicroorganisms. Quaternary ammonium compounds denature the proteins ofthe bacterial or fungal cell, affect the metabolic reactions of the celland allow vital substances to leak out of the cell, finally causingdeath.

Most uses of quaternary ammonium compounds as antimicrobials involveformulations of disinfectants and sanitizers which are not bound to asurface, resulting in effluent stream pollution and contamination. Theyare simply wetted onto the surface such as in disinfecting wipes whichare primarily ammonium. salts as their liquid active ingredient. Whenthey are incorporated into surfaces they are not crosslinked but areallowed to float to the surface thereby becoming depleted over time thesame way silver and triclosan are incorporated in plastics. Couplingquaternary ammonium compounds to a surface or formation within a polymermatrix may inherently reduce the effectiveness of the quaternaryammonium compounds, by decreasing the accessibility of microbes to themost active cationic portion of the molecule. Increasing accessibilityto the quaternary ammonium compounds within a surface coating or withany use increases the effectiveness of the quaternary ammonium compound.

In some embodiments, the effectiveness of an antimicrobial (e.g.,quaternary ammonium compound) may be increased by coupling theantimicrobial within or on a curved surface, where the curved surface ison a molecular scale. For example, a curved surface may be created usingnanoparticles (e.g., spherical nanoparticles). Nanoparticles mayincorporate into their structure antimicrobial compounds with greaterexposed surface area due to the curved surface of the nanoparticle.

In some embodiments, a compound may include a nanoparticle. Thenanoparticle may include a bridged polycyclic compound. A compound maybe formed using self-assembly techniques and principles. A compound maybe formed from portions which are themselves antimicrobial (e.g.,quaternary ammonium compounds). A compound may bind moieties to at leastportions of itself which have, for example, antimicrobial properties.

In some embodiments, a protective coating composition may include acompound. A compound may be a bridged polycyclic compound. A bridgedpolycyclic compound may be a cavitand. Portions of the bridgedpolycyclic compound may include two or more quaternary ammoniummoieties. The protective coating composition may be antimicrobial.

In some embodiments, a composition may include one or more bridgedpolycyclic compounds. At least one of the bridged polycyclic compoundsmay include at least two cyclic groups. A general example of a bridgedpolycylic compound including only two cyclic groups may include, but isnot limited to, a compound 100 having a general structure

In some embodiments, at least two cyclic groups may be defined in partby quaternary ammonium moieties, by the nitrogen of the quaternaryammonium moiety comprising one of the atoms which forms a part of thecyclic structure itself. For example, a cyclic structure which is formedat least in part by a quaternary ammonium moiety may include, but is notlimited to structure 101

Structure 101 is an example of quaternary ammonium moieties defining atleast in part a cyclic group, however, compound 101 is not an example ofa polycyclic compound and compound 101 is not an example of a bridgedpolycyclic compound.

In some embodiments, a bridged polycyclic compound may include at leasttwo quaternary ammonium moieties, at least three quaternary ammoniummoieties, at least four quaternary ammonium moieties, at least fivequaternary ammonium moieties, at least six quaternary ammonium moieties,at least seven quaternary ammonium moieties, or at least eightquaternary ammonium moieties.

In some embodiments, a compound 100 may have a general structure

Compound 100 may be formed by coupling a trifunctional corner unit Awith a bifunctional linker unit L as depicted in Scheme 2.

Scheme 2 should not be used as to limit the disclosure set forth herein.Corner unit A may include multiple dentate linkers other than the onedepicted in Scheme 2 (e.g., a trifunctional linker A is depicted inScheme 2) including, but not limited to, bifunctional, tetrafunctional(e.g., compound 100a) etc. In some embodiments, a corner unit A may becoupled to a linker unit L in any multitude of ways known to one skilledin the art.

In some embodiments, a compound 100c may have a general structure

Compound 100c may be a bridged polycyclic compound. Compound 100c may beantimicrobial. In some embodiments, Z may include at least one bridge.Bridge Z may couple 2 non adjacent atoms.

In some embodiments, at least one of the bridges is —R²—N⁺R³ ₂—R⁴—N⁺R³₂—R²—, such that each bridge independently couples A to A. In someembodiments, at least one of the bridges may be —R²—N⁺R³ ₂ —R⁴—N⁺R³₂—R²—. Each bridge may independently couple A to A. In some embodiments,at least one of the bridges may be —R²—NR³—R⁴—N⁺R³ ₂—R²—. Each bridgemay independently couple A to A. In some embodiments, at least one ofthe bridges may be —R²—N═R⁴═N—R²—. Each bridge may independently coupleA to A.

For example when Z is 1 compound 100c may be a compound 100 having ageneral structure

When, for example, Z is 2 a compound 100c may be a compound 100a havinga general structure

When, for example, Z is 2 a compound 100c may be a compound 100d havinga general structure

In some embodiments, a compound may include a bridged polycycliccompound formed from two corner units (e.g., compound 100b). Compound100b may be formed by coupling a multifunctional (e.g., trifunctional)corner unit A with a second multifunctional (e.g., trifunctional) cornerunit A as depicted in Scheme 2 a.

In some embodiments, a compound 102 may have a general structure

Compound 102 may include a moiety coupling corner unit A with linkerunit L, the moiety including a nitrogen.

In some embodiments, a compound 103 may have a general structure

In some embodiments, R¹ may be independently alkyl, substituted alkyl,aryl, substituted aryl, N, N⁺R³, heterocycle, or substitutedheterocycle. R² may be independently alkyl, substituted alkyl, aryl,substituted aryl, heterocycle, substituted heterocycle, covalent bond,or alkene. R³ may be independently alkyl, substituted alkyl, aryl,substituted aryl, heterocycle, substituted heterocycle, alkene, ether,PEG, or PEI. R⁴ may be independently alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alkylether, PEG, PEI, ether, or alkene. R⁴ may independently include amide,alcohol, ester, sulfonamide, or sulfanilamide. R⁴ may be independentlyalkyl, substituted alkyl, aryl, substituted aryl, heterocycle,substituted heterocycle, ether, amide, alcohol, ester, sulfonamide,sulfanilamide, or alkene. X may be one or more counter ions. Z mayinclude at least one bridge.

In some embodiments, at least one of the bridges may be —R²—N⁺R³₂—R⁴—N⁺R³ ₂—R²—. Each bridge may independently couple R¹ to R¹. In someembodiments, at least one of the bridges may be —R²—NR³—R⁴—N⁺R³ ₂—R²—.Each bridge may independently couple R¹ to R¹. In some embodiments, atleast one of the bridges may be —R²—NR³—R⁴—NR³—R²—. Each bridge mayindependently couple R¹to R¹. In some embodiments, at least one of thebridges may be —R²—N═R⁴ ═N—R²—. Each bridge may independently couple R¹to R¹.

For example when Z is 1 compound 103 may be a compound 104 having ageneral structure

When, for example, Z is 2 a compound 103 may be a compound 104 a havinga general structure

In some embodiments, a compound 104 may have a general structure

In some embodiments, R¹ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, or substituted heterocycle. R² maybe alkyl, substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, covalent bond, or alkene. R³ may be alkyl,substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, alkyl ether, PEG, PEI, or alkene. R⁴ may bealkyl, substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, alkyl ether, PEG, PEI, ether, or alkene. R⁴ mayinclude amide, alcohol, ester, sulfonamide, or sulfanilamide. X may beone or more counter ions.

In some embodiments, counterions may include one or more halogens (e.g.,Br, Cl, I, etc.). A specific embodiment of a halogen counterion mayinclude Iodine which has proven as a more effective counterion forbridged polycyclic antimicrobial compounds. As has been discussedherein, counterions may affect the properties of the chemical compoundand subsequent composition. Boron based counterions may increase certainantimicrobial properties (e.g., BF₄ ⁻).

In some embodiments, salts of specific counterions may be added to anantimicrobial composition to increase the effectiveness of thecomposition. For example, any of the counterions described herein foruse in making the bridged polycyclic compound (e.g., counterions whichincrease the antimicrobial effectiveness of the compound), may be addedto the composition later (e.g., as a salt such as sodium or potassiumtetrafluoroborate). In some embodiments, a combination of the twostrategies may be used, additionally allowing for two or more differentcounterions or salts to be included in the final formulation of thecomposition. Each of the counterions and/or salts may increase theantimicrobial effectiveness of the composition in a different manner.Other examples of counterions (which may be added as an appropriate saltlater) may include an anion, a polymer, a monomer, a halogen, an iodine,a bromine, a chlorine, a triflate, a tosylate, a boron, a borate,tetrafluoroborate, a nitrogen containing gourp, a nitrate, a halogen, ahexafluorophosphate, or an NTf₂ (wherein Tf isbis(trifluoromethanesulfonyl)imide).

In some embodiments, a compound may include one or more guest moleculescoupled to the compound such as compound 106 having a general structure

In some embodiments, R¹ may be alkyl, substituted alkyl, aryl,substituted aryl, N, N⁺R³, heterocycle, or substituted heterocycle. R²may be alkyl, substituted alkyl, aryl, substituted aryl, N⁺R³,heterocycle, substituted heterocycle, covalent bond, or alkene. R³ maybe alkyl, substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, alkyl ether, PEG, PEI, or alkene. R⁴ may bealkyl, substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, alkyl ether, PEG, PEI, ether, or alkene. M mayinclude one or more guest molecules associated with one or more portionsof compound 107 (e.g., amines). M may be one or more metals. M mayinclude silver, zinc, copper, gold, calcium, nickel, cobalt, barium,strontium, lead, lanthanum, iron, manganese, cadmium, magnesium,yttrium, lanthanum, cesium, praseodymium, neodymium, europium,gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, oralkaline earth metals or cesium. In some embodiments, M may includeorganic cation salts as templates (e.g., trimethyl ammonium, etc.). Mmay include light activated elements such that an antimicrobial propertyof M is increased. X may be one or more counter ions.

In some embodiments, M may be one or more guest molecules. X may be oneor more counter ions. M (e.g., Ag+ counter ion) may bind thereby keepingM in close proximity (e.g., F-ions have been reported and verified byx-ray single crystal structure to bind in ammonium salt cavitands). Ananion may bind to an ammonium thus affording a close association of thecation counterion. In some embodiments, M may pi-bond coordinate to R₄(e.g., aryl) or a heterocycle binding (e.g., pyridiyl R₄ nitrogen to aAg+ or a phenol —OH or O-binding to the Ag+).

In some embodiments, M may be two silver metals associated with compound107 forming a compound 107 a having the general structure

In some embodiments, a compound may include one or more guest moleculescoupled to the compound such as compound 108 having a general structure

In some embodiments, R¹ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, or substituted heterocycle. R² maybe alkyl, substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, covalent bond, or alkene. R³ may be alkyl,substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, alkyl ether, PEG, PEI, or alkene. R⁴ may bealkyl, substituted alkyl, aryl, substituted aryl, N⁺R³, heterocycle,substituted heterocycle, alkyl ether, PEG, PEI, ether, or alkene. M maybe one or more metals. M may include silver, zinc, copper, gold,calcium, nickel, cobalt, barium, strontium, lead, lanthanum, iron,manganese, cadmium, magnesium, yttrium, lanthanum, cesium, praseodymium,neodymium, europium, gadolinium, terbium, dysprosium, holmium, erbium,thulium, ytterbium, or alkaline earth metals or cesium. In someembodiments, M may include organic cation salts as templates (e.g.,trirethyl ammonium, etc.). M may include light activated elements suchthat an antimicrobial property of M is increased. X may be one or morecounter ions.

It should be understood that any of the compounds depicted herein may ormay not have one or more metals coupled to the structure. For example, astructure depicted with a metal associated with the compound alsoincludes a compound without a metal associated with the compound. Astructure depicted without a metal associated with the compound alsoincludes a compound with a metal associated with the compound. Althoughin many instances metals depicted herein are shown positioned within aspace defined by compounds described herein, this should not be seen aslimiting, metals may be coupled (e.g., complexed to) to a compound alongan outer surface of the compound.

Metals may include any elements in the periodic chart designated asmetals, known to one skilled in the art. In some embodiments, metals mayinclude any cationic metal known to one skilled in the art (e.g., Zn,Cu, Au, Ag, Cs, Mn, Mg, Ca, Ni, Co, etc.). In some embodiments, metalsmay include metals which have antimicrobial properties and/oranti-inflammatory properties (e.g., Ag, Zn, etc.). In some embodiments,metals may function to couple one or more atoms or molecules within acompound (e.g., compound 108) and/or to the surface of the compound. Insome embodiments, one or more metals coupled to a compound may includeone or more inorganic/organometallic compounds. A compound (e.g., abridged polycyclic compound) may include two or more different metalscoupled (e.g., associated in some way) to the compound. In someembodiments, a metal may be coupled to a bridged polycyclic molecule.

In some embodiments, R¹ may be N⁺(1-22C alkyl), N⁺(1-12C alkyl), N⁺(1-6Calkyl), N⁺(6C alkyl), N⁺R³,

cyclam, aza crown ether, tris ethylamine N substituted cyclam, or

In some embodiments, R² may be 1-2C alkyl, 1-6C alkyl, 2-4C alkyl, CH₂,or a bond (e.g., covalent, ionic) between R¹ and a N of, for example,compound 108.

In some embodiments, R³ may be hydrophobic or hydrophilic. R³ may be1-3C alkyl, 4-5C alkyl, 6-10C alkyl, 7-9C alkyl, 10-22C alkyl, 15-22Calkyl, 6-10C alkyl ether, 7-9C alkyl ether, methyl, PEI(polyethyleneimine), or PEG (polyethyleneglycol). R³ may be 6C alkyl. R³may be a polymer. R³ may be an oxazoline polymer.

In some embodiments, R⁴ may be an aryl, substituted aryl, heterocycle,or substituted heterocycle. R⁴ may

Forming one or more portions of a compound from one or more aromaticrings may provide advantages.

Advantages may include providing rigidity to the compound enhancing thestability of the compound. Aromatic rings may facilitate theself-assembly of the constituent parts of the compound. Other advantagesmay include pie stacking of compounds relative to one another or of“guests” positioned within the compound. A substituted aryl orheterocycle may include moieties (e.g., N) which bind to other elements(e.g., metals such as silver) or molecules.

R⁴ may include substituents (e.g., R³) which effect properties of acompound as a whole (e.g., hydrophobicity, hydrophilicity,self-cleaning, antimicrobial, cross-coupling properties).

In some embodiments, a compound 108 may include an embodiment such ascompound 110 having a general structure

In some embodiments, R³ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alkylether, PEG, PEI, or alkene. R⁴ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alkylether, PEG, PEI, ether, or alkene. M may include one or more “guest”molecules (e.g., one or more metals). X may be one or more counter ions.

In some embodiments, M may be two silver metals associated with compound110 forming a compound 112 having the general structure

In some embodiments, R³ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alcylether, PEG, PEI, or alkene. R⁴ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alkylether, PEG, PEI, ether, or alkene. M may be one or more guest molecules.X may be one or more counter ions. M (e.g., Ag+ counter ion) may bindthereby keeping M in close proximity (e.g., F-ions have been reportedand verified by x-ray single crystal structure to bind in ammonium saltbridged polycyclic molecules). An anion may bind to an ammonium thusaffording a close association of the cation counterion. In someembodiments, M may pi-bond coordinate to R⁴ (e.g., aryl) or aheterocycle binding (e.g., pyridiyl R⁴ nitrogen to a Ag+ or a phenol —OHor O-binding to the Ag+).

In some embodiments, a compound 104 may include an embodiment such ascompound 111 having a general structure

In some embodiments, a compound 104 may include any number ofcombination of embodiments such as compound 113 having a generalstructure

-   -   Where:    -   113a is R^(3.1)═C₆H₁₃, R^(3.2)═CH₃ and R^(3.3)═R^(3.1) or        R^(3.2)    -   113b is R^(3.1)═C₈H₁₇, R^(3.2)═CH₃ and R^(3.3)═R^(3.1) or        R^(3.2)    -   113c is R^(3.1)═C₁₀H₂₁, R^(3.2)═CH₃ and R^(3.3)═R^(3.1) or        R^(3.2)    -   113d is R^(3.1)═C₁₂H₂₅, R^(3.2)═CH₃ and R^(3.3)═R^(3.1) or        R^(3.2)    -   113e is R^(3.1)═C₆H₁₃, R^(3.2)═CH₂Ph and R^(3.3)═R^(3.1) or        R^(3.2)    -   113f is R^(3.1)═C₁₂H₂₅, R^(3.2)═CH₂Ph and R^(3.3)═R^(3.1) or        R^(3.2)    -   113h is R^(3.1)═C₄H₉, R^(3.2)═CH₃ and R ^(3.3)═R^(3.1) or        R^(3.2)

In some embodiments, a compound 104 may include a an embodiment such ascompound 114 having a general structure

In some embodiments, R³ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alkylether, PEG, PEI, or alkene. R⁴ may be alkyl, substituted alkyl, aryl,substituted aryl, N⁺R³, heterocycle, substituted heterocycle, alkylether, PEG, PEI, ether, or alkene. M may be one or more metals. X may beone or more counter ions.

Substituents (e.g., R³) may be configured to perform a variety offunctions. By using different substituents, properties of a compoundsuch as the bridged polycyclic compounds described herein may becustomized to meet a particular industrial and/or individual's need. Forexample, R³ may be hydrophobic or hydrophilic depending upon thespecific property needed.

In some embodiments, a substituent (e.g., R³) may be multifunctionalsuch that it imparts two or more properties to a formed compound. Forexample a substituent (e.g., R³) may function to increase thehydrophilicity of a compound, as well as, function as a cross-couplingreagent to cross-link compounds to one another under appropriateconditions (e.g., a substituent may include one or more heteroatomswithin its structure such as N, O, and S).

In some embodiments, substituents such as R³ may function to enhancehydrophobicity and/or lipophilicity. Depending upon the needs of acustomer the hydrophobicity/lipophilicity of a compound may beincreased. Adjusting the hydrophobicity/lipophilicity of a compound mayconsequently adjust the solubility of the compound in a particularsolvent and/or matrix. Increasing the liphophilicity of a substituent(e.g., R³) coupled to an ammonium salt may increase the anti-microbialactivity of a compound. In some embodiments, a compound may have aminimum inhibitory concentration (MIC) of less than 900 μM, of less than600 μM, or of less than 300 μM. A discussion of relationship betweensubstituent chain length and antimicrobial activity of quaternaryammonium salts may be found in Pernak et al., “Synthesis andanti-microbial activities of some pyridinium salts with alkoxymethylhydrophobic group” Eur. J. Med. Chem. 36 (2001) 899-907, which isincorporated by reference as if fully set forth herein.

The relationship between substituent chain length and antimicrobialactivity is demonstrated in tests conducted on 113a, 113b, 113d, 113e,and 113h detailed herein in the Examples portion. A series of bridgedpolycyclic compounds were synthesized wherein different substituentswere coupled to the quaternary ammonium moieties. Substituents includedC1, C4, C6, C8, C12, and benzyl in combinations of C1 with C4, C6, C8,and C12, as well as, combinations of benzyl with C6 and C12. Time killand residual surface tests of the antimicrobial strength of thecompounds were tested against examples of gram+bacteria (e.g.,Staphylococcus aureus, most common surgical wound infection),gram—bacteria (e.g., Escherichia coli, most commonly acquired hospitalinfection), and fungus (e.g., Aspergillus niger, a toxic black moldfound in residences). Of the various alkyl chains combined with C1tested, the C6, C1 compound tested as the strongest antimicrobialcompound. When the test results of the C6, C1 were compared to thebenzyl derivatives, once again, the C6,C1 derivative tested as theoverall strongest antimicrobial.

The 113a C6C1 compound is unique in regards to the relatively shortalkyl chain vs. known quaternary antimicrobials and high antimicrobialactivity. Discrete quaternary ammonium or pyridinium antimicrobialmolecules usually possess long alkyl chains. The most effective discrete(e.g., noncyclic) quaternary ammonium or pyridinium salt antimicrobialshave an alkyl chain length between 12 and 18 carbon atoms as describedby T. Loftsson et. al. in J. Med. Chem. 46, 2003, 4173-4181, which isincorporated by reference as if fully set forth herein.

In general it is known in the art that quaternary ammonium compounds areeffective biocidal agents when they possess an alkyl chain with at leasteight carbon atoms (S. Block, ‘Disinfection, Sterilization andPreservation’, 3^(rd)Ed., Lea and Febiger, Philadelphia, Pa., 1983;cited in ‘Recent Advances in Antimicrobial Dendrimers’, S. L. Cooper et.al. Adv. Mater. 2000, 12, no. 11, 843-846, which is incorporated byreference as if fully set forth herein). In a study of dendrimerquaternary ammonium salts, dendriter biocides carrying C₁₀ alkyl chainswere the most potent (S. L. Cooper et.al. Biomacromolecules, 1 (3), 473480, 2000), which is incorporated by reference as if fully set forthherein.

Typically, non-discrete polymers are some of the only antimicrobials toshow any appreciable antimicrobial activity with alkyl groups of <8carbons. However, non-discrete polymers (e.g. polyethyleneiminequaternary ammonium containing polymers) demonstrated weaker overallantimicrobial activity in antimicrobial residual surface tests (A. M.Klibanov et.al. Biotechnology Letters, 25, 2003, 1661-1665), which isincorporated by reference as if fully set forth herein.

Furthermore, the straightforward route and synthesis efficiency makesbridged polycyclic compounds (e.g., 113a) more attractive from amanufacturing standpoint over the more laborious methods required fortypical dendrimer synthesis. Both bridged polycyclic compounds (e.g.,113a) and dendrimers have the advantage of being polyvalent (multiplepositively charged sites on one molecule to attract microbes) affordingincreased activity vs. traditional discrete quaternary ammonium salts(S. L. Cooper et. al. U.S. Pat. No. 6,440,405). However, the dendrimersynthesis requires large volumes of solvents/reagents relative toobtained product and long periods of time (days) to synthesize asdescribed by S. L. Cooper et. al. in U.S. Pat. No. 6,440,405, which isincorporated by reference as if fully set forth herein.

In some embodiments, substituents such as R³ may function to enhancehydrophilicity and/or lipophobicity. Depending upon the needs of acustomer the hydrophilicity/lipophobicity of a bridged polycycliccompound may be increased. Adjusting the hydrophilicity/lipophobicity ofa compound may consequently adjust the solubility of the compound in aparticular solvent and/or matrix.

In some embodiments, substituents such as R³ may function to enhance theself-cleaning properties of which the compound may impart to a surfaceto which the compound is coupled. In some embodiments, substituents mayenhance the antimicrobial properties of the compound. Self-cleaning andantimicrobial properties may function in combination with one another.

The search for self-cleaning surfaces has come about from theobservation of such surfaces occurring naturally in nature, such aslotus leaves. To clean a surface, material has to be transported alongit, and best, off it. By tuning the wettability of the substrate, twobasic options arise. The surface may be rendered very wettable, and thedecontamination process is based on film flow. But, interestingly,biology hints at a different option. Non-wettable plant leaf surfaces,such as those of the famous Lotus plant, have a built-in elementarycleaning mechanism. This was noticed in the mid-nineties by botanistsstudying plant surfaces. They observed that droplets running off theleaves may carry dry contaminants along—the origin for the Lotus leaf 'sstatus as a sacred object of purity. It is widely held thatself-cleaning surfaces are a combination of low surface-energy speciesand a peculiar topographic feature based on dual-size roughness: thecoarse-scale rough structure is about 10-20 μm, whereas the finerstructure on top of the coarse structure is in the range of 100 nm to 1μm. The dual-size structure has proven to be vital in generating thesuperhydrophobicity of the lotus leaves, especially for obtaining lowwater rolloff angles. Techniques for forming superhydrophobic surfacesmay be found in Ming et al., “Superhydrophobic Films from Raspberry-likeParticles” Nano Lett., 5 (11), 2298-2301, 2005, which is incorporated byreference as if fully set forth herein.

In some embodiments, a first compound described herein may include aplurality of second compounds coupled to the surface of the firstcompound. The first compound may be several times larger than the secondcompound. The first compound may be an order of magnitude or larger thanthe second compound. The first compound may include, but is not limitedto, compounds such as compound 100 Second compounds may be coupled toactive sites on the first compound to form a third compound. In someembodiments, the second compound may include, but is not limited to,compounds such as compound 100, coupled to active sites of a firstcompound. Coupling the third compound to a surface may provide thenecessary surface topography (e.g., a dual-roughness) to produce aself-cleaning surface.

In some embodiments, a topology of a surface treated with the coatingcompositions described herein may have at least one layer havingelevations whose average height may be from 20 nm to 25 μm and whoseaverage separation is from 20 nm to 25 μm, whose average height is from50 nm to 10 μm and/or whose average separation is from 50 nm to 10 μm,or whose average height is from 50 nm to 4 μm and/or whose averageseparation is from 50 nm to 4 μm. The topology of a surface treated withthe coating compositions described herein may have elevations whoseaverage height is from 0.25 to 1 μm and whose average separation is from0.25 to 1 μm. The average separation of the elevations is the separationbetween the highest elevation of an elevation and the most adjacenthighest elevation. If an elevation has the shape of a cone, the tip ofthe cone is the highest elevation of the elevation. If the elevation isa rectangular parallelepid, the uppermost surface of the rectangularparallelepid is the highest elevation of the elevation.

In some embodiments, a hydrophobic coating may be applied over aprotective coating including a self-cleaning topological surface.

In some embodiments, substituents (e.g., R³) coupled to portions of acompound may function as the finer structure relative to the coarserstructure of the compounds. Substituents such as R³ may increase thehydrophobicity of the compounds to which the substituents are coupled.

However, a disadvantage of the hydrophobic surfaces is that if thestructures are sufficiently complicated, (e.g., moldings with undercutsor porous moldings or sponges, water may not then penetrate these voids)the result being that the cleaning properties of the surface may beinhibited. The globular shape of the water droplets on these surfacesmay cause visual impairment if the droplets do not roll off from thesurface because the surface is, for example, horizontal. In suchinstances, highly wettable surfaces may be advantageous, since a waterdroplet on these becomes distributed over almost the entire surface andforms a film of minimum thickness. This occurs in particular if thesurface tension of the water is reduced by appropriate means (e.g.,surfactants) and/or a hydrophilic surface is present. In someembodiments, hydrophilic substituents (e.g., R³) may be coupled toactive sites (e.g., amines) on compounds described herein. In someembodiments, hydrophilic substituents/coatings (e.g., hydrophilicsilicas) may be coupled to compounds described herein. A discussion ofhydrophilic substances and particles may be found in U.S. PatentApplication, Publication No. 20050118911 to Oles et al. (“Oles”), whichis incorporated by reference as if fully set forth herein. Increasingthe hydrophilicity of a surface may inhibit microbial adhesion.Substituents for inhibiting microbial adhesion may be found in Ming etal., “Bacterial Adhesion at Synthetic Surfaces” APPLIED ANDENVIRONMENTAL MICROBIOLOGY, November 1999, p. 4995-5002, which isincorporated by reference as if fully set forth herein.

A self-cleaning surface including compounds may be enhanced bydecreasing the surface energy or increasing the hydrophobicity of theself-cleaning surface. Several different techniques may be used incombination with compounds to increase the hydrophobicity andself-cleaning properties of a surface.

In some embodiments, a surface may be first coated with a hydrophobicsubstance (e.g., a hydrophobic polymer) and followed by applyingcompounds to the coating. The hydrophobic substance may be a matrixwhich also reacts with active sites on provided compounds (e.g., siloxybased polymers). In some embodiments, compounds may be dispersed withina matrix before applying the matrix to a surface. The matrix may act asa low energy hydrophobic coating which also couples the compounds to thesurface after curing the matrix.

In some embodiments, counter ions for a bridged polycyclic compound maybe selected to adjust particular properties of a compound or tointroduce new properties to the compound. Adjusting properties of acompound based on a selection of a particular counter ion allows furthercustomization of a compound. In some embodiments, counter ions mayinclude counter ions which have or enhance antimicrobial propertiesand/or anti-inflammatory properties (e.g., boron, zinc). In someembodiment, counter ions may adjust the hydrophilicity or hydrophobicityof the complex. Counter ions may include metals. Research has held thatspecific counter ions do affect the antimicrobial activity of quaternaryammonium compounds.

Counter ions may include, but are not limited to, organic, inorganic, ororganometallic moieties. Examples of counter ions may include inorganicions (e.g., halogen ions, such as fluorine, bromine, chlorine andiodine), organic ions (e.g., tosylate, prosylate sulfuric acid, nitricacid and phosphoric acid, and ions of organic acids such as succinicacid, fumaric acid, lactic acid, glycolic acid, citric acid, tartaricacid and benzoic acid), or coordinate type anions (e.g., fluoro sulfateand tetrafluoro borate).

In some embodiments, counter ions may include a hydrophobic organicgroup (e.g., lauryl sulfate, dodecylbenzene sulphonate, diethylhexylsulphosuccinate, carboxylic acid derivatives with alkane, alkene oralkyne aliphatic tails such as myristic acid salts, octadecanate,dodecanoic acid salts, oleic acid salts, Palmitoleic acid salts, lauricacid salts, Stearic acid salts, phosphinic acid salts, phosphonic acidsalts (i.e. tetradecylphosphonate, hexadecylphosphonate) anddodecylsulphonate, dodecylsulfate anions).

Synthesis of Bridged Polycyclic Compounds

For commercialization purposes compounds such as bridged polycycliccompounds (and their metal and/or metal oxide coated counterparts)require an efficient and cost effective method of synthesis. In someembodiments, bridged polycyclic compounds may be formed through theself-assembly of two or more compounds to form much larger complexsystem in fewer steps and more efficiently than traditional stepwisesynthetic means.

At the most general level, the words “self-assembly” are used toidentify the phenomenon whereby some kind of higher-level patternemerges from the interactions of multiple simple components. An exampleof self-assembly from the Stang group is shown in Scheme 1 (Stang, P.J.; Cao, D. H. J. Am. Chem. Soc. 1994, 116, 4981). To set thisparticular type of self-assembly in its proper context, it should benoted that in the field of chemistry, the term “self-assembly” is usedto describe two distinct types of processes. On the one hand, there areassemblies that lead to the formation of essentially infinite arrays,while on the other hand, there are assemblies such as that shown inScheme 1 that lead to distinct, bounded species. Furthermore, withineach of these categories, it is possible to make a further distinctionthat reflects the scale of organization. For example, for infinitearrays, one may consider processes such as crystallization, where themolecules are ordered at the molecular level (ca. 10⁻⁹ m), or theformation of self-assembled monolayers and bilayers, where there islittle order between individual molecules, but a larger scale oforganization is evident across say the 10⁻⁶ m level. Likewise, the scaleof organization for assemblies leading to distinct species may be brokendown into similar categories. It may be noted the self-assembly ofmacroscale objects (10⁻³ m) is currently being investigated. However, asfar as the interaction of molecules to form distinct species goes, itmay be considered the formation of micelles and vesicles thatconstitutes assembly at the 10⁻⁶ m level.

The essential features of chemical assembly processes is that they sharea common self-correcting mechanism. In other words, strictself-assemblies are fully reversible, dynamic, systems that lead to aproduct that represents the global thermodynamic minimum for the system.Sometimes an additive or template is needed to boost the efficiency ofthe assembly, but this is the only true variable if one is speaking ofstrict self-assembly. At their cores, strict molecular assembliesconsist of subunits, product, and an equilibrium that relates the two.

One addition to the assembly lexicon added a layer of complexity to theabove definition. Thus, one of the seven different classes ofself-assembly originally proposed by Lindsey—which are strictself-assembly processes (with or without a template) positioned indifferent chemical settings—is commonly known as “irreversibleself-assembly.” This term is used to describe two-step processes,whereby a strict self-assembly processes is followed by irreversiblereactions that covalently knit together the array of subunits. AsWhitesides noted, strictly speaking this term is a misnomer. Hence,along with other types of post-assembly modified self-assemblies, onecategorizes these processes as “self-assembly with covalentmodification.” Postmodification generally comes in the form of a seriesof covalent bond formation steps and is of less interest to us here. Thecrux of any self-assembly process is the self-assembly.

Even within the strict confines given above, self-assembly processescome in all shapes and sizes. One of the results of this complexity isthat defining self-assembly is difficult. Thus, although definitionsfrom Hamilton, Whitesides, and Lehn were highly influential inclarifying the quality of self-assembly, signs of confusion still appearin the literature. Perhaps part of the problem lies in Kelvin's dictum:if we cannot put a number to it, we do not understand it. Put anotherway, without a unifying quantitative description of self-assembly, one'sappreciation of self-assembly is limited. With the idea of a unifyingquantitative description of self-assemblies, Lehn pointed out that one'sapproach must require a kind of molecular information science, of“molecular informatics.” Hence, chemists have, over the last 15 years orso, been busy contributing to this information data bank. As thiscollection of data increases, it becomes possible to begin to quantifyassemblies. This process is, in effect, writing the rule book that willultimately allow molecular subunits to be readily designed andsynthesized for a required self-assembly. A discussion of supramolecularself-assembly using covalent bonds may be found in Bruce C. Gibb “StrictSelf-Assembly and Self-Assembly with Covalent Modifications”Encyclopedia of Supramolecular Chemistry 17 Aug. 2004, which isincorporated by reference as if fully set forth herein.

Dynamic covalent chemistry relates to chemical reactions carried outreversibly under conditions of equilibrium control. The reversiblenature of the reactions introduces the prospects of “error checking” and“proof-reading” into synthetic processes where dynamic covalentchemistry operates. Since the formation of products occurs underthermodynamic control, product distributions depend only on the relativestabilities of the final products. In kinetically controlled reactions,however, it is the free energy differences between the transition statesleading to the products that determines their relative proportions.Supramolecular chemistry has had a huge impact on synthesis at twolevels: one is noncovalent synthesis, or strict self-assembly, and theother is supramolecular assistance to molecular synthesis, also referredto as self-assembly followed by covalent modification. Noncovalentsynthesis has given us access to finite supermolecules and infinitesupramolecular arrays. Supramolecular assistance to covalent synthesishas been exploited in the construction of more-complex systems, such asinterlocked molecular compounds (for example, catenanes and rotaxanes)as well as container molecules (molecular capsules). The appealingprospect of also synthesizing these types of compounds with complexmolecular architectures using reversible covalent bond forming chemistryhas led to the development of dynamic covalent chemistry. Historically,dynamic covalent chemistry has played a central role in the developmentof conformational analysis by opening up the possibility to be able toequilibrate configurational isomers, sometimes with base (for example,esters) and sometimes with acid (for example, acetals). Thesestereochemical “balancing acts” revealed another major advantage thatdynamic covalent chemistry offers the chemist, which is not so easilyaccessible in the kinetically controlled regime: the ability tore-adjust the product distribution of a reaction, even once the initialproducts have been formed, by changing the reaction's environment (forexample, concentration, temperature, presence or absence of a template).This highly transparent, yet tremendously subtle, characteristic ofdynamic covalent chemistry has led to key discoveries in polymerchemistry. A discussion of supramolecular self-assembly may be found inRowan, S. J. et al. “Dynamic covalent chemistry” Angew Chem Int EdEngl., 2002 Mar. 15; 41(6):898-952, which is incorporated by referenceas if set forth herein.

In some embodiments, self-assembly techniques (e.g., dynamic covalentchemistry) may be employed to synthesize stable compounds, which arethemselves large enough to be described as nanoparticles and/or whichmay be used to form nanoparticles.

Bridged polycyclic compounds represented by compounds 104 and 108 may besynthesized by any means known to one skilled in the art. As has beenmentioned, self-assembly may be a useful technique for efficientlysynthesizing nanoparticles described herein. In some embodiments,nanoparticles such as compounds 104 and 108 may be formed viaself-assembly using Schiff base condensation reactions between aminesand aldehydes to form an imine as depicted in Scheme 3.

In Scheme 3, the amine depicted is trifunctional and the aldehyde isbifunctional. However, the example depicted in Scheme 3 should not beseen as a limiting embodiment. For example, a Schiff base condensationreaction is depicted in Scheme 4 in which the amine is bifunctional andthe aldehyde is trifunctional.

In some embodiments, two different trifunctional molecules may bereacted with one another in order to form an asymmetric adduct. Scheme4a depicts an embodiment of the formation of an asymmetric adduct.

For example, a trifunctional amine (e.g., tris(2-aminoethyl)amine(TREN)) may be reacted with a trifunctional aldehyde (e.g.,1,3,5-aldehyde substituted phenyl). Triethanolamine may befunctionalized at the OH with an aminoacid to giveN—(CH₂CH₂OC(O)Phenyl(CHO). N—(CH₂CH₂OC(O)Phenyl(CHO) may be reacted withany triamine to give an asymmetric example of a bridged polycycliccompound. A discussion of synthesis techniques for differentmultifunctional ligands (e.g., trifunctional aldehydes) may be found inChand et al. “Synthesis of a Heteroditopic Cryptand Capable of Imposinga Distorted Coordination Geometry onto Cu(II): Crystal Structures of theCryptand (L), [Cu(L)(CN)](picrate), and [Cu(L)(NCS)] {picrate) andSpectroscopic Studies of the Cu(II) Complexes” Inorg Chem 1996, 35,3380-3387, which is incorporated by reference as if fully set forthherein.

In some embodiments, formation of a bridged polycyclic compound (e.g.,Schemes 4, 4a, or 5) may be carried out in an alcohol (e.g., ethanol).

A more specific example of the self-assembly Schiff base condensationstrategy depicted in Scheme 3 is depicted in Scheme 5 showing theformation of imine compound 116. Imine compound 116 may be used as anintermediate toward the formation of compound 110.

A Schiff base condensation may be carried out using an acid catalyst(e.g., acetic acid). A Schiff base condensation may be carried out usingany means known to one skilled in the art. Techniques for amine aldehydecondensations may be found in U.S. Patent Application, Publication No.2004/0267009 to Redko et al. (“Redko”), which is incorporated byreference as if fully set forth herein.

Other examples of Schiff base condensations may include reactions suchas those depicted in Scheme 5a. Scheme 5a depicts a substituted aminecondensing with an aldehyde.

In some embodiments, a template may be used to facilitate the formationof compounds such as 118. A template may include a metal template. Ametal template may include any metal cation. A template may assist inpreorganizing one or more reagents in a Schiff base condensation suchthat labile reagents are properly oriented to form a bridged polycycliccompound as opposed to an oligomer, facilitating the reaction. Scheme 6depicts a schematic representation of the formation of a compound 118using such a strategy.

In some embodiments, compound 118 may be used as an intermediate towardthe formation of a bridged polycyclic compound (e.g., compound 110).Techniques for template facilitated synthesis of molecules may be foundin Drew et al., “d¹⁰ Cations within triple-helical cryptand hosts; astructural and modeling study” J. Chem. Soc., Dalton Trans., 2000,1513-1519, which is incorporated by reference as if fully set forthherein.

When a metal template is used in the formation of a bridged polycycliccompound (e.g., compound 118), the template may be carried through therest of the synthesis. In some embodiments, a metal template may bereplaced in a later transmetallation step. It may be more efficient toconsider all of the properties of the metal template so that atransmetallation step is not necessary at a later time. Not only may ametal's templating ability for a condensation reaction be considered butwhether or not the metal also has antimicrobial or anti-inflammationproperties.

Schiff base condensation chemistry should not be viewed as a limitingexample of a method for forming bridged polycyclic compounds asdescribed herein. There exist many other methods of forming bridgedpolycyclic compounds as described herein. Other types of condensationreactions are known. Scheme 6a depicts an embodiment of a condensationreaction which may be used to form a bridged polycyclic compound (e.g.,compound 118a).

Techniques for the synthesis of molecules using condensation reactionsas generally depicted in Scheme 6a may be found in Xiao-an Zhang, “FromSupramolecular Vanadate Receptors to Enzyme Models of VanadiumHaloperoxidase” Philosophisch-Naturwissenschaftlichen Fakultät derUniversität Basel, 2005, which is incorporated by reference as if fullyset forth herein. Compound 118a may be further reduced to the thiol(e.g., thioether, including peptides and/or peptide mimics and/oraziridines), alkylated, metalated, and/or used as a core for acore-shell compound.

In some embodiments, imine compounds (e.g., 7 and 8) may be reduced toan amine (e.g., a secondary amine). Schemes 7 and 8 depictrepresentations of the reductions of two different imine compounds totheir respective amines. Schemes 7 and 8 depict the reduction of allimines in compounds 116 and 118, however in some instances this may notbe desirable and only some of the imines may be reduced to preserve atleast some of the imine functional groups for later exploitation.

Reduction techniques are well known to one skilled in the art, and thereare many reductions techniques known to one skilled in the art which maybe applied. Some common reductive reagents include, but are not limitedto, LiAlH₄, NaBH₄, H₂, or polymethylhydrosiloxane (PMHS). Some compoundssuch as PMHS may be used with a lewis acid (e.g., B(C₆H₅)₃, ZnCl₂, BF₃,AlCl₃, Zn-diamine, Ti(O^(i)Pr)₄, IrCl[COD]₂, IrCl[COE]₂, RhCl[COD]₂,IrCl₃, Ti(OR)₄, Ti(CO₂OR)₄, Ti(ester)₄, Ti(amine)₄, CuI, Cu(OAc)₂,etc.). Methods for using PMHS as a reducing agent may be found inLawrence et al., “Polymethylhydrosiloxane: a versatile reducing agentfor organic synthesis” J. Chem. Soc., Perkin Trans. 1, 1999, 3381-3391,which is incorporated by reference as if fully set forth herein.

In some embodiments, a reduction may be carried out in an alcohol (e.g.,ethanol) with with a reducing agent (e.g., sodium borohydride).

In some embodiments, coupling of corner units or corner units and linkerunits to form bridged polycyclic imine compounds may be carried out inan alcohol (e.g., ethanol) based solvent. In some embodiments, reductionof at least some of the imines may be carried out without anysubstantial work up directly following the coupling step (e.g., byadding a reducing agent such as sodium borohydride) to form a bridgedpolycyclic compound.

In the past reactions such as the coupling and reduction steps have beencarried out as two totally separate steps involving for example workingup (e.g., purifying and isolating) the reaction after the coupling stepbefore the reducing step. One or more of these steps (e.g., the couplingstep) have in the past been carried out in for example acetonitrileresulting in a seemingly polymeric substance, followed by an isoxolateextraction. In reality the isoxolate extraction may have been merelydriving the reaction towards the bridged polyclic product, by conversionof polymer and oligomer products.

Running the reactions in a solution of heated ethanol results in almostquantitative yields of the desired product without any substantial workup or isolation protocols.

In some embodiments, coupling of corner units or corner units and linkerunits to form bridged polycyclic imine compounds may be carried out in agreen solvent. In some embodiments, a green solvent may include anysolvent which is naturally occurring and which has been found not toharm the environment when used on an industrial scale. In someembodiments, a green solvent may include water or an alcohol basedsolvent (e.g., ethanol). A catalyst may be used to run the reaction inwater. In some embodiments a catalyst may include aniline. A similarmethod is described in Angewante Chemie Vol. 45, pages 75-81, which isincorporated by reference as if fully set forth herein.

In some embodiments, certain industrial wastes may be used as a hydridesource for reducing an imine to an amine. Using an industrial waste mayhave several advantages. Using industrial wastes as reactive reagentsmay be environmentally friendly due to the recycling of waste which mustnormally be disposed. Industrial wastes are normally very inexpensive,if not free, and sometimes companies will pay for them to be removed.Some industrial wastes may be used as a matrix for the bridgedpolycyclic compounds facilitating application of the bridged polycycliccompounds to surfaces.

In some embodiments, one or more amines of a bridged polycyclic compoundmay transformed into the corresponding ammonium salt. A precursor of asubstituent R³ may be reacted with an amine of a bridged polycycliccompound forming quaternary ammonium salts. In some embodiments, X of aprecursor may include a halogen (e.g., alkyl bromide). A base, morespecifically a weak base, may be used in combination with for example analkyl bromide. A portion of a precursor of a substituent R³ may act as acounter ion X. A nonlimiting example may include reacting compound 120with bromohexane in the presence of a base (e.g., triethylamine) formingan amine alkylated with the hexyl and the resulting bromine ion acts asat least one of the counter ions X to compound 124. It is to beunderstood that counter ions may be exchanged at a later point in asynthetic sequence to a more desirable counter ion (e.g., a counter ionthat can demonstrate increased antimicrobial properties compared toother halide counterions) using methods known to one skilled in the art.A counterion of this type is tetrafluoroborate. Tetrafluoroborate can bereadily exchanged for iodide by adding potassium tetrafluoroborate to asolution of an iodide salt in common solvents known to those skilled inthe art as described by A.D. Headley, et. al. in J. Org. Chem. 2006,ASAP received Jun. 27, 2006, which is incorporated by reference as iffully set forth herein. Ion exchange is a common technique and can alsobe found in D. F. Bocian Inorg. Chem. 1998, 37, 1191-1201 and S. T.Diver J. Org. Chem. 2002, 67, 1708-1711, which is incorporated byreference as if fully set forth herein. Schemes 9 and 10 depict theformation of quaternary ammonium salt compounds 124 and 126.

Common techniques for functionalizing amines may be found in a review bySalvatore et al., “Synthesis of secondary amines” Tetrahedron 57, 2001,7785-7811, which is incorporated by reference as if fully set forthherein.

In some embodiments, an amine may be functionalized (e.g., compound 122)by reacting with an epoxide. For example, reacting compound 122 with anepoxide may result in an epoxide ring opening and thus a free alcoholcoupled to at least some of the amines in compound 122. The resultingfree alcohol may be reacted with (OR)₃Si(CH₂)_(n)N⁺R₃ resulting from theattack of the N on the epoxide containing carbon. This may result in anammonium on the bridged polycyclic compound and an ammonium pendant arm.Free amines of the herein described bridged polycyclic compounds may bereacted with a di-epoxide crosslinker (e.g., 1,2,7,8-diepoxyoctane orepoxypropyl terminated polydimethylsiloxane), followed by(OR)₃Si(CH₂)_(n)N⁺R₃ to functionalize the crosslinked mixture. Reactionwith a vinyl epoxide may result in a light crosslink terminus and analcohol (e.g., with which a silane may be reacted). A free amine of abridged polycyclic compound described herein may be modified by an epoxyalkane (or glycidyl ether (e.g., hexyl, octyl or decyl glycidyl ether)),followed by further modification by a variety of alkoxysilanes withdesired functional groups (e.g., an alkyl ammonium salt attached to theSi). One may modify a free amine with alkyl anhydrides (e.g.,2-octen-1-ylsuccinic anhydride).

In another example of functionalizing an amine at least in part defininga bridged polycyclic compound, a functionalized substituent may becoupled to the amine. A functionalized substituent may include an alkylamine group. A non-limiting example of an alkyl amine may include—CH₂CH₂CH₂NH(CH₂)₅CH₃. The amine may be further functionalized. Forexample the amine of the alkyl amine may be alklyated such that anotherquaternary amine is available increasing the antimicrobial activity ofthe bridged polycyclic compound. The synthesis of such an embodiment isdetailed in the Examples section.

As mentioned previously, it is widely held that self-cleaning surfacesare a combination of low surface-energy species and a peculiartopographic feature based on dual-size roughness: the coarse-scale roughstructure is about 10-20 μm, whereas the finer structure on top of thecoarse structure is in the range of 100 nm to 1 μm. The dual-sizestructure has proven to be vital in generating the superhydrophobicityof the lotus leaves, especially for obtaining low water rolloff angles.In some embodiments, free amines of a bridged polycyclic compound asdescribed herein may be mixed with an oxide bridged polycyclic compound(e.g., TiO₂ or SiO₂), followed by a di-epoxide linker (e.g.,1,2,7,8-diepoxyoctane or epoxypropyl terminated polydimethylsiloxane)and a photo activated crosslink (e.g., N-vinyl-2-pyrrolidinone). Adiscussion of the reaction of epoxides, oxides, amines, etc. may befound in Trentler et al., “Epoxy Resin-Photopolymer Composites forVolume Holography” Chem. Mater. 2000, 12, 1431-1438, which isincorporated by reference as if fully set forth herein. There are manymethods for cross-linking bridged polycyclic compounds which may alsolead to the desired topography necessary for superhydrophobicity,including crosslinking oxide bridged polycyclic compounds withsilsesquioxanes. A discussion of the reaction of epoxides (e.g., vinylepoxides), silsesquioxanes, etc. may be found in Huang et al.,“Thermomechanical properties of polyimide-epoxy nanocomposites fromcubic silsesquioxane epoxides” J. Mater. Chem. 2004, 14, 2858-2863,which is incorporated by reference as if fully set forth herein. Generaltechniques (e.g., using Michael-type additions) forfunctionalizing/modifying the surface of particles (which may be appliedto bridged polycyclic compounds as described herein) may be found inU.S. Pat. No. 6,887,517 to Cook et al. (“Cook”), which is incorporatedby reference as if fully set forth herein.

In some embodiments, one or more amines of a bridged polycyclic compoundmay be functionalized in more than one step. For example, severalsecondary amines forming a bridged polycyclic compound may betransformed into tertiary amines, followed by subsequent transformationinto a quaternary amine. Such synthetic flexibility allows customizationof the amines such that different functional groups may be coupled tothe same amine. Depending on the reactions conditions required to couplethe different functional groups to the amine, the reactions may be runsequentially without any purification steps between coupling differentfunctional groups to the amine. Scheme 11 depicts a genericrepresentation of a two step functionalization sequence of the secondaryamines of compound 120 to form the quaternary ammonium salts of compound128. In the first step bromohexane and a nonnucleophilic base (e.g.,triethylamine) are added to the reaction mixture, followed by theaddition of methyliodide and more triethylamine to form compound 128such that several of the quaternary amrnmonium salts include twodifferent functional groups. The ability to customize the functionalgroups attached to the quaternary ammonium salt is important at least inthat the functional groups attached to a quaternary ammonium salt mayeffect the antimicrobial properties of the salt. Customization offunctional groups attached to bridged polycyclic compounds, and aminesspecifically, may allow coupling of functional groups with differentfunctionalities (e.g., groups which function to cross-couple bridgedpolycyclic compounds to one another or to a surface.

Metal Oxide Coatings of Bridged polycyclic Compounds

Nanocrystals of transition metal oxides have attracted a great deal ofattention from researchers in various fields due to their numeroustechnological applications. Among them, titanja (TiO₂) nanocrystals havebeen the most intensively studied owing to their versatile applications,which include solar cells, photocatalysts, and photochromic devices.Many synthetic methods have been reported for the preparation of TiO₂nanocrystals, including sol-gel reactions, hydrotherrnal reactions,nonhydrolytic sol-gel reactions, template methods, and reactions inreverse micelles. TiO₂ nanocrystals with various morphologies andshapes, such as nanorods, nanotubes, nanowires, and nanospheres may beproduced depending on the synthetic method used.

Due to the high reactivity of titanium precursors such as TiCl₄andtitanium alkoxides, the control of the reaction rate is a key factor inobtaining TiO₂ nanocrystals with the desired crystalline structureand/or shapes. Chemseddine and co-workers have reported the synthesis ofuniform-sized TiO₂ nanocrystals whose shapes varied depending on theratio of Me₄NOH to titanium alkoxide. However, the synthesis wasperformed at a very low concentration and produced only a small quantityof the nanocrystals. Weller and co-workers have reported the controlledgrowth of TiO₂ nanocrystals by modulation of the hydrolysis rate, usingoleic acid as a stabilizing surfactant at 80° C., and Jun et al. havereported the surfactant-mediated shape evolution of anatase nanocrystalsin nonaqueous media at 300° C. Techniques for low temperature synthesisof metal oxide and metal oxide shells may be found in Han et al.,“Low-Temperature Synthesis of Highly Crystalline TiO₂ Nanocrystals andtheir Application to Photocatalysis” Small, 1, No. 8-9, 812-816, andImihof et. al. “Preparation and Characterization of Titania-CoatedPolystyrene Spheres and Hollow Titania Shells” Langmuir, 17, 3579-3585,which are incorporated by reference as if fuilly set forth herein.

Additionally Core-shell metal nanoparticles is an emerging and activearea of contemporary science. While most of the research in this areahas been on noble-metal nanocores and molecular shells, there has been aslow and steady growth of activity on nanomaterials with chalcogenideshells. Monolayers anchored onto metal cores have been used asprecursors to make oxide shells. An approach in this direction has beenused to make silica-coated gold clusters. Similar method have been usedin the synthesis of ZrO₂-covered nanoparticles of silver. In all thesemethodologies, the monolayer cover is important, as the chemistry isspecific to the shell. Previous monolayer routes to oxide-shellmaterials are rather involved and requires multistep processes, andscale-up is difficult. More recently a one step method was developedusing the well-known reduction of noble metals with dimethylformamide(DMF) in the presence of oxide-forming precursors used by Liz-Marzan etal. for the synthesis of Ag@TiO₂. Using this method TiO₂- andZrO₂-covered Au and Ag redissolvable particles were synthesized. Workwas initiated on oxide-protected metal colloids because this is one wayto make metal nanoparticles stable under extreme conditions. Recent workon optical nonlinearity has shown that these materials are some of thebest optical limiters known thus far. However, at high lightintensities, they are susceptible to damage, leading tophotofragmentation, ligand desorption, etc. To make them stable atextreme conditions, it is necessary to protect them with stable andchemically inert shells such as oxides. Oxide-protected colloids wereirradiated with laser pulses of intensities up to 2.8GW/cm₂, and no signof laser-induced damage was observed. This kind of cover also makes itpossible to fabricate/process materials in the form of thin films anddisks for applications. Particles with oxide shells are interesting fromother perspectives as well. The catalytic properties of the oxidesurfaces, modified with the metal core, especially photocatalysis, arean important aspect. The shells being porous at low thickness makes itpossible for ions and molecules to diffuse through them. Apart fromimplications in catalysis, this also leads to changes in the dielectricconstant, which results in changes in color. Modified properties such aselectrical transport upon exposure to gases and ions are anotherimportant aspect. The shell being inert may be used to deliver metalcolloids into reactive environments and may even be thought of as a modeto deliver drugs. From all these perspectives, it is interesting andpossibly desirable to make core-shell particles with oxide covers bysimple and scalable procedures. Techniques for synthesizing metal oxideshells may be found in Tom et al., “Freely Dispersible Au@TiO2, Au@ZrO2,Ag@TiO2, and Ag@ZrO2 Core-Shell Nanoparticles: One-Step Synthesis,Characterization, Spectroscopy, and Optical Limiting Properties”Langmuir 2003, 19, 3439-3445, which is incorporated by reference as iffully set forth herein.

Coating of colloidal particles with a layer of a different material isused as a means to modify their surface chemical, reactive, catalytic,optical, or magnetic properties. Such core-shell particles may often beprepared by controlled precipitation of inorganic precursors onto thecore particles, in some cases assisted by a coupling agent as with thecombination silica and gold or silver as described above. A secondapproach is to deposit small particles of the coating material on thecores by heterocoagulation, such as in the case of yttrium basiccarbonate or zirconia on polystyrene.

An especially versatile example of the second approach is thelayer-by-layer technique, in which successive layers of anionicparticles are deposited, alternated by layers of a cationic polymer. Thelayer-by-layer technique has the great advantage that it is not veryspecific for the coating material, where other methods usually depend onthe particular combination of core and shell material. Disadvantages arethat the layers are added in discrete steps of about 30 nm and that alot of redundant polymer is also incorporated in the shell. Hollowparticles form a special kind of core-shell particle in which the coreconsists of air or solvent. Hollow inorganic particles are made byremoval of the core with a solvent or by heating (calcination). Removalof polystyrene cores by calcination has been used to make hollow spheresof yttrium compounds, zirconia, and silica. Hollow silica particles havebeen made by dissolution of silver and gold or zinc sulfide. Colloidalcrystals of particles with a low-index core and a high-index shell suchas titania are suitable building blocks for photonic crystals, providedthat they may be made monodisperse with a smooth coating.

Particles coated with titania are generally exceptionally difficult tosynthesize because the titania precursors are highly reactive, making itdifficult to control their precipitation. This easily causes the coreparticles to aggregate or the titania to form separate particles.Titania coated particles are very useful as catalysts and as whitepigments. Titanyl sulfate in sulfuric acid was used to deposit titaniaon silica spheres. Rather irregular coatings were obtained. The slightlylow isoelectric point indicated that the coverage was incomplete. Thiswas also found to be the case by using TiCl₄ to coat silica. Othermethods use the hydrolysis of titanium alkoxides in nonaqueous solventsas the precursor. Only a monolayer of titania was deposited on silicaspheres in tetrahydrofuran. Using a similar approach, thicker coatingsmay be deposited on copper compounds, zinc oxide, silica, and goldnanoparticles. These methods lead to particles with a complete coatingbut with a lot of surface roughness. They also take place at a ratherlow concentration of the alkoxide, typically around 0.01 M. Thisconcentration needs to be well controlled because too highconcentrations easily lead to particle aggregation or formation ofsecondary titania particles. This is why multiple steps are often usedto obtain thicker coatings.

Stable colloidal core-shell particles consisting of a polystyrene coreand a titania coating were prepared in one step by the hydrolysis of atitanium alkoxide in the presence of a cationic polystyrene latex.Although Imhof used polystyrene as a core, other polymer colloids may begiven cationic surface groups or negatively charged particles may bemade positive by coating with a polyelectrolyte. The coatings are verysmooth and uniform and may be varied in thickness from just a fewnanometers to at least 50 nm. Thicker coatings should also be possiblebut only through a multistep seeded growth process. The coated sphereshave the same monodispersity as the starting latex, allowing them toform colloidal crystals.

Measurement of the coating thickness with light scattering and electronmicroscopy showed that the titania coating is not dense when theparticles are in suspension in ethanol but that it densifies when theparticles are dried. From the ratio of titania to polystyrene, measuredby thermogravimetric analysis, it was found that the coating consists of21 vol % titania and that drying increases this to 55 vol %. In theprocess, the shells become much thinner.

Hollow titania particles may be made by removal of the polystyrene coreseither by dissolution in toluene or by firing in a furnace. Thedissolution route leaves stable colloidal titania shells that arespherical and monodisperse. Drying of these shells causes them to deformbecause of their softness. The firing route produces dense, undeformedshells of a mosaic of small anatase crystallites. Techniques forsynthesis of metal oxide shells may be found in Han et al.,“Low-Temperature Synthesis of Highly Crystalline TiO₂ Nanocrystals andtheir Application to Photocatalysis” Small, 1, No. 8-9, 812-816, whichis incorporated by reference as if fully set forth herein.

The antimicrobial effects of titanium dioxide have been known for quitesome time and it is used to control bacteria activity. When titaniumdioxide (TiO₂) is irradiated with near-UV light, this semiconductorexhibits strong bactericidal activity. In some embodiments, cationicbridged polycyclic compounds described herein may be used as thecationic core of a core-shell particle. The shell may be formed formnegatively charged metal oxides deposited on the surface of thepositively charged core bridged polycyclic compound. By combining metaloxides (e.g., TiO₂) with positively charged bridged polycyclic compoundscontaining quaternary ammonium salts, one is able to combine theproperties of both substances (e.g., different mechanisms ofantimicrobial attack within one bridged polycyclic compound leading to amore effective antimicrobial).

In some embodiments, a positively charged or neutral bridged polycycliccompound core may be coated with any metal and/or metal oxide. An oxideprecursor of the metal oxide coating may be used to deposit the metaloxide shell around the bridged polycyclic compound core. An oxideprecursor may include, but is not limited to, a metal halogenate (e.g.,TiCl₄) or a metal alkoxide (e.g., titanium tetraisopropoxide (TTIP)). Ametal alkoxide may be more stable. In some embodiments, any metalprecursor may be used to coat a charged bridged polycyclic compound corewith an oxide shell.

In some embodiments, any metal and/or metal precursor may be used tocoat a bridged polycyclic compound core. For example, silver may becoupled to the exterior of a bridged polycyclic compound (e.g., silvermay coat a portion and/or substantially all of the exterior of thebridged polycyclic compound). In some embodiments, a metal oxide shellmay be formed/deposited around a bridged polycyclic compound core and/ora bridged polycyclic compound core including a metal (e.g., silver)coating.

Metals which may be deposited on a charged or neutral core include, butare not limited to Ti, Zr, Hf, B, Zn, Ta, W, V, or combinations thereof(e.g., TiOZrO, borotitanate, etc.). Examples such as these are alsobiologically active and may contribute to the antimicrobial and/oranti-inflammatory nature of the core-shell bridged polycyclic compoundscreated. Shell oxides may contribute to a core-shell bridged polycycliccompounds self-cleaning properties.

In some embodiments, metal oxide bridged polycyclic compounds and/ormetal oxide core-shell bridged polycyclic compounds may be formed frommain group metals, transition group metals, or lanthanide metals. Maingroup metals may include, but are not limited to, aluminum, gallium,germanium, indium, tin, antimony, lead, and bismuth.

Transition metals may include, but are not limited to, titanium,vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc,yttrium, zirconium, niobium, molybdenum, ruthenium, rhodium, cadmium,hafnium, tantalum, tungsten, rhenium, osmium, and iridium.

Lanthanide metals may include, but are not limited to, lanthanum,cerium, praseodymium, neodymium, samarium, europium, gadolinium,terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium.

In some embodiments, alkaline earth metals (e.g., calcium, strontium,and barium) may generally be one metal component in mixed metal oxides(e.g., calcium titanate, calcium ruthenate, barium titanate, bariumruthenate, strontium titanate, strontium ruthenate, yttrium bariumcopper oxide). Simple oxides such as MgO and SrO may be prepared by thismethod.

In some embodiments, alkali metals (e.g., lithium and potassium) maygenerally be one metal component in mixed metal oxides (e.g., lithiumtantalate (LiTaO₃), lithium niobate (LiNbO₃), Fe- or Ti-doped lithiumniobate, potassium barium niobate (KBa₂Nb₅O₁₅), potassium lithiumniobate (K₃Li₂Nb₅O₁₅), potassium sodium tantalate ((K_(1-x)Na_(x))TaO₃),K₃Li₂(Ta_(x)Nb_(1-x))₅O₁₅ etc.).

In some embodiments, a metal M may include CaBi₂O₄. CaBi₂O₄ is anantimicrobial substance activated by natural light, providing anothercustomization avenue, as opposed to titanium oxides which areantimicrobial upon activation by ultraviolet light.

The composition, e.g., solution, used for the deposition includes thesoluble polymer and the metal precursors. Metals may be included throughaddition of appropriate metal salts. For example, barium may be addedthrough a barium salt such as barium acetate. Suitable metal salts mayinclude metal nitrates, metal oxalates, metal acrylates, and metalcoordination complexes.

Titanium oxides have been mentioned several times due to their welldocumented properties (e.g., antimicrobial) as well as the fact thattitanium is inexpensive when compared to other metals. However, thereare many other metals which may be used and/or combinations of metalswhich may provide added advantages not observed using any one metal byitself.

In some embodiments, combinations of metals may be used to form a mixedmetal oxide shell around a bridged polycyclic compound core. In someembodiments, metal oxide films may include, but are not limited to, ametal oxide with a single metal, may be a metal oxide with two metals orthree metals or may be a metal oxide including four or more metals.Mixed oxides have been widely used in catalysis, because the propertiesof the individual oxides may be modified by the presence of neighboringphases. Mixed oxides improve the activity and selectivity of catalystsby means of the formation of surface defects that may give rise to theformation of acid or basic sites. In semiconductors mixed oxides haveimportant role in modifying the electrical or optical properties of theisolated oxides. Usually zirconia and titania are mixed by solid statereaction, requiring temperatures as high as 2000° C. to form thecrystalline ZrTiO₄. Mixed metal oxides may include, but are not limitedto, barium titanium oxide (barium titanate), strontium titanium oxide(strontium titanate), barium strontium titanium oxide (barium strontiumtitanate), strontium ruthenium oxide (strontium ruthenate),lanthanum-strontium manganese oxide, yttrium-barium-copper oxide(YBa₂Cu₃O₇), vanadium-barium-titanate, etc. The antimicrobial coatingsprepared by the present process may be insulating, resistive,conductive, ferroelectric, ferromagnetic, piezoelectric, and evensuperconductive depending upon the chemical compositions and microstructures.

Gomez et al. reported the synthesis of sol-gel catalysts, where theprecursors of the sol-gel catalysts were titanium n-butoxide (98%,Aldrich) and zirconium n-butoxide (99%, Aldrich), with n-butanol (Baker,99%) as solvent. Samples were prepared by mixing 3.3 moles of H₂O and3.0 moles of n-butanol at 0° C. under constant stirring. After adjustingthe pH at 3 with HNO₃, titanium and zirconium n-butoxide were addeddrop-by-drop to the initial solution for five hours, appropriatedamounts of the corresponding alkoxides were used to obtain 100, 90 50,10 and 0 wt % of TiO₂ in ZrO₂. The resulting suspensions were maintainedunder reflux and constant stirring until gelling. Samples were thendried at 70° C. for 24 hours (fresh samples) and calcined at 600 for 4h. The 2,4-dinitroaniline photodecomposition was determined at roomtemperature. The evolution of the 2,4-dinitroaniline decomposition infunction of time was followed with a UVV is spectrometer at fixedabsorption band of 346 nm.

When the diffraction patterns of the pure titania samples are comparedwith those of the samples containing 10 wt % ZrO₂, no phase associatedwith pure zirconia was observed, only anatase and rutile wereidentified. This means that the 10 wt % of ZrO₂ was dissolved in thesetwo titania polymorphs. The incorporation of zirconium atoms intoanatase stabilized the crystalline anatase structure (99 wt %). Anadditional effect of zirconium atoms is to reduce the crystallite sizeof both anatase (50 to 13 nm) and rutile phases (90 to 49 nm). Thesample with 50:50 wt % amounts of titania and zirconia shows amorphousand crystalline ZrTiO₄ phase with mean crystallite size of 1.1 and 36 nmrespectively. The crystalline ZrTiO₄ phase corresponds to the onlyintermediate compound reported for this system, Gomez et al.'s resultsshow that the non-hydrolytic synthesis method is not a condition toobtain the compound without previous segregation of tinania or zirconiaas reported elsewhere. The samples of pure zirconia and that with 10 wt% titania were amorphous after synthesis. The unmixed ZrO crystallized48 wt % into the tetragonal phase and the 52 wt % into the monoclinicphase. In the rich ZrO₂ mixed oxide only tetragonal and mocliniczirconia may be observed, hence titania was dissolved in the tetragonaland monoclinic phases of zirconia. The crystallite size of thetetragonal phase in the 10 wt % TiO₂ sample is 15 nm and is of the sameorder to that corresponding to the phase obtained in unmixed zirconia(13 nm). This result indicates that titania inhibits crystallitegrowing; this is also valid for the monoclinic phase. This resultcontrasts with the observed effect of zirconia into the crystallizationof the titania polymorphs diminishing the TiO₂ crystallite size. Gomezet al. then assumed that ZrTiO₄ is a semiconductor, which generatesimportant hole-electron mobility between the conduction band and thevalence band improving the photoactivity. Techniques for synthesis ofmixed metal oxide shells may be found in Gomez et al., “Synthesis,characterization and photocativity of nanosized sol-gel TiO₂—ZrO₂ mixedoxides.” The 13th International Congress on Catalysis, Jul. 10-15, 2004,Paris, France, which is incorporated by reference as if fully set forthherein.

In some embodiments, stabilizers may be before/during/after coating acharged bridged polycyclic compound with a metal oxide. Stabilizers maybe added before/during the reaction to ensure the formation of a smoothcoating and to prevent the formation of secondary titania particles.After the reaction is complete any or excess stabilizers may be removed.Stabilizers may also be chosen to customize the solubility of theoxide-coated bridged polycyclic compounds. Hydrophilic stabilizers(e.g., polyethylene glycol (PEG), PEG derivatives) may be chosen toincrease the water solubility of the new core-shell bridged polycycliccompound. Hydrophobic stabilizers may be used to increase the solubilityof the core-shell bridged polycyclic compound in hydrophobic solvents.This may be necessary depending upon the desired properties of thecore-shell bridged polycyclic compound. The shell may be so thick thatsubstituents (e.g., R³) on the surface of a bridged polycyclic compoundcore may not be able to effect the properties of the core-shell bridgedpolycyclic compound, thus increasing the need for functional stabilizersubstituents coupled to the surface of the core-shell bridged polycycliccompound.

In some embodiments, stabilizers may be used simply to ensure theuniformity of coating of the shell over the core. After completion ofthe reaction the stabilizers may be removed upon work-up (e.g.,purification) of the core-shell bridged polycyclic compounds.

By modifying the conditions of the reaction during the formation of theshell around the core bridged polycyclic compound, many of theproperties (e.g., uniformity and thickness) of the shell may becontrolled. Metal oxide shells are known to be porous at low thickness.The shells being porous at low thickness makes it possible for ions andmolecules to diffuse through them. Contact of a microbe cell wall and acore-shell bridged polycyclic compound may cause part of the microbecell wall to open and diffuse into the bridged polycyclic compound,depending upon the specific properties of the shell. In this waycore-shell bridged polycyclic compounds may be customized to exposemicrobes to two or more types of compounds with antimicrobialproperties. Preparing antimicrobials including two or more antimicrobialfunctionalities may increase the effective killing power of thecore-shell bridged polycyclic compound towards microbes.

In some embodiments, reaction conditions during formation of the oxideshell around a core bridged polycyclic compound may be controlled suchthat different products and/or different product ratios are obtained.For example, by increasing the concentration of the reaction, metaloxide bridged polycyclic compounds may be formed alongside core-shellbridged polycyclic compounds. Adjusting the concentration may adjust theratio of metal oxide bridged polycyclic compounds to core-shell bridgedpolycyclic compounds. By decreasing the concentration of the reaction,only a portion of a core bridged polycyclic compound may covered with anoxide shell. Forming “core-(partial)shell bridged polycyclic compounds”may allow the resulting bridged polycyclic compound to displayproperties typically exhibited by the core and shell separately. Forming“core-(partial)shell bridged polycyclic compounds” may allow furtherflexibility and customization of a coating including the bridgedpolycyclic compounds.

Matrices and Methods of Coating a Surface

In some embodiments, a bridged polycyclic compound (e.g., compound 100,core-shell bridged polycyclic compound) may be suspended within amatrix. A matrix may include a polymeric composition and/or prepolymericcompounds. In some embodiments, a matrix may be formed by cross couplingbridged polycyclic compounds. A matrix is typically composed of one ormore monomers, but may include other matrix components/constituents.Often the matrix constituents include one or more “addressable”components or complementary binding pairs, that optionally promoteassembly and/or cross-linkage of the matrix. Techniques for combiningcompounds with an appropriate matrix and applying said matrix to asurface may be found in U.S. Pat. No. 6,929,705 to Meyers et al.(“Meyers”), U.S. Patent Application, Publication No. 2005/0008777 toMcCleskey et al. (“McCleskey”), and U.S. Patent Application, PublicationNo. 2005/0008763 to Schachter (“Schachter”), which are incorporated byreference as if fully set forth herein.

A wide variety of nanostructure-compatible polymers are known to thoseof skill in the art (see e.g., Demus et al. (ed.) 1998 Handbook ofLiquid Crystals Volumes 1-4, John Wiley and Sons, Inc., Hoboken, N.J.);Brandrup (ed.) 1999 Polymer Handbook, (John Wiley and Sons, Inc.);Harper 2002 Handbook of Plastics, Elastomers, and Composites, 4thedition (McGraw-Hill, Columbus, Ohio); and Kraft et al. (1998) Angew.Chem. Int. Ed. 37:402-428.

Exemplary polymers which may be used include, but are not limited to,thermoplastic polymers (e.g., polyalkenes, polyesters, polysilicones,polyacrylonitrile resins, polystyrene resins, polyvinyl chloride,polyvinylidene chloride, polyvinyl acetate, or fluoroplastics);thermosetting polymers (e.g., phenolic resins, urea resins, melamineresins, epoxy resins, polyurethane resins); engineering plastics (e.g.,polyamides, polyacrylate resins, polyketones, polyimides, polysulfones,polycarbonates, polyacetals); and liquid crystal polymers, includingmain chain liquid crystal polymers (e.g., poly(hydroxynapthoic acid))and side chain liquid crystal polymers (e.g.,poly[n-((4′(4″-cyanphenyl)phenoxy)alkyl)vinyl ether]).

-   1. Some specific embodiments of polymers which may be used in a    matrix to support bridged polycyclic compounds may include, but are    not limited to, aminoacrylic resins, epoxy resins, and polyurethane    resins. Organic polymeric materials used for forming    antibiotic-containing films or coatings may include any synthetic,    natural or semi-synthetic organic polymers so far as they may be    formed into films. Generally, such polymers are thermoplastic    polymers or thermoset polymers. Examples of such organic polymeric    materials include, but are not limited to, acetate rayon, acrylic    resins, acrylonitrile-butadiene-styrene (ABS) resins and acrylic    resins, aliphatic and aromatic polyamides, aliphatic and aromatic    polyesters, allyl resin, (Allyl), AS resins, butadiene resins,    chlorinated polyethylene, conductive resins, copolymerised    polyamides, copolymers of ethylene and vinyl acetate, cuprammonium    rayons and natural and synthetic rubbers, EEA resins, epoxy resins    (e.g., bisphenol, dihydroxyphenol, and novolak), ether ketone    resins, ethylene vinyl alcohol, (ENVAL), fluorine resins,    fluorocarbon polymers, fluoroplastics, (PTFE), (FEP, PFA, CTFE,    ECTFE, ETFE), high density polyethyelenes, ionomer resins, liquid    crystal polymer, (LCP), low density polyethylenes, melamine    formaldehyde, (melamine resins), natural polymers such as    cellulosics, nylons, phenol-formaldehyde plastic, (PF) phenolic    resins, polyacetal, (acetal), polyacrylates, (acrylic),    polyacrylonitrile, (PAN), (acrylonitrile), polyamide, (PA), (nylon),    polyamide-imide, (PAI), polyaryletherketone, (PAEK), (ketone),    polybutadiene, (PBD), polybutylene terephthalate, polybutylene,    (PB), polycarbonate, (PC), polycarbonates, polydicyclopentadiene,    (PDCP), polyketones, (PK), polyester block copolymers, polyesters,    polyesterurethane, polyesterurethaneurea, polyether and polyester    block polymers, polyether ketoneketone (PEKK), polyetherether ketone    (PEEK), polyetherimide, (PEI), polyethers, polyethersulfone, (PES),    polyetherurethane, polyetherurethaneurea, polyethylene isophthalate,    polyethylene terephthalate, polyethylene, (PE),    polyethylenechlorinates, (PEC), polyglycolic acid, polyhexamethylene    terephthalate, polyimide, (PI), polylactic acid, polymethylpentene,    (PMP), polyvinyl alcohol, polymethyl methacrylate,    polymethyl-co-polybutyl methacrylate, poly-m-phenylene    isophthalamide, polyalkenes, polyphenylene oxide, (PPO),    polyphenylene sulfide, (PPS), polyphthalamide, (PTA),    poly-p-phenylene terephthalamide, polypropylene, (PP), polysiloxanes    such as polydimethyl siloxane, polystyrene, (PS), polysulfides,    polysulfone, (PSU), polytetrafluoroethylene, polyurethane, (PU),    polyvinyl acetate, polyvinyl alcohols, polyvinylchloride, (PVC),    polyvinylidene chloride, (PVDC), polyvinylidene fluoride and    polyvinyl fluoride, rayon, reconstituted silk and polysaccharides,    reinforced polyethylene terephthalate resins, segmented polyurethane    elastomers, silicone resins, spandex or elastane elastomers, styrene    type specific resins, thermoplastic polyurethane elastomers,    thermosetting synthetic polymers such as phenol-formaldehyde    copolymer, triacetate rayon, unsaturated polyester resins, urea    resins, urethane resins, vinyl chloride resins, vinyl polymers, and    vinylidene chloride resins. This group includes reasonable    copolymers, terpolymers and mixtures of the species listed.

In some embodiments, matrices may include polymers such as polyethers.Polyethers may include poly(arylene) ethers. Examples of, as well as,methods of making polyethers may be found in U.S. Pat. Nos. 5,658,994and 5,874,516 to Burgoyne, Jr. et al. (“Burgoyne”); U.S. Pat. No.6,080,170 to Nash et al. (“Nash”); U.S. Pat. No. 6,187,248 to O'Neill etal. (“O'Neill”); and U.S. Pat. No. 6,716,955 to Burgoyne, Jr.(“Burgoyne”), which are incorporated by reference as if fully set forthherein.

In some embodiments, matrices may include polymers based on acrylicemulsions. Examples of, as well as, methods of making acrylic emulsionsand their use in fast dry and extremely durable waterborne, coatingcomposition may be found in U.S. Pat. No. 5,824,734 to Yang (“Yang”),which is incorporated by reference as if fully set forth herein.

In some embodiments, polyurethane/vinyl polymers and copolymers may beemployed to form improved coating dispersions used for forming a matrixfor compounds described herein. The hybrid polymer coating dispersionsoffer benefits in shelf stability, self-cross-linkability,surfactant-free nature, water resistance, and low temperaturecross-linking. Methods for making such aqueous polyurethane-vinylpolymer dispersion may be found in U.S. Pat. No. 5,521,246 to Tien etal. (“Tien”) and U.S. Pat. No. 6,218,455 to Smith et al. (“Smith”),which are incorporated by reference as if fully set forth herein.

In some embodiments, methods for making shelf stable epoxy polymerhybrid water-based dispersions may include (1) polymerizing anunsaturated monomer in the presence of an epoxy resin in water, and (2)blending a separately prepared vinyl acetate based polymer dispersionwith a liquid epoxy resin and isophoronediarnine. The resulting epoxyhybrid dispersions may be useful as protective film coatings andadhesives. A benefit of the technology in method 1 may be the potentialof the prepared hybrid dispersion to be combined later withpolyfunctional amine curatives and remain a stable one-pot dispersionsystem. A benefit of method 2 may be its potential to yield a stableone-pot dispersion system as prepared. Methods for making such aqueouspolyurethane-vinyl polymer dispersion may be found in U.S. Pat. No.5,389,703 to Lee (“Lee”) and U.S. Pat. No. 6,235,811 to Robeson et al.(“Robeson”), which are incorporated by reference as if fully set forthherein.

In some embodiments, 3-trimethoxy silyl propyl dimethyl octadecylammonium chloride may serve as a matrix for the coatings describedherein. When 3-trimethoxy silyl propyl dimethyl octadecyl ammoniumchloride is used as a matrix, it may be activated, for example, withhydrolysis.

In some embodiments, reagents and/or matrices may serve dual purposes.Certain compounds may be used as reagents for forming bridged polycycliccompounds described herein as well as acting as a matrix for the bridgedpolycyclic compounds. For example PMHS may be used as a reductive agentduring the synthesis of bridged polycyclic compounds (e.g., compounds120 and 122) and PMHS may then act as a matrix by cross-linking thereduced bridged polycyclic compounds.

Polymers may be dissolved in suitable solvents or in some cases,dispersed in a suitable liquid or solvent mixture. This may includewater. Examples of organic solvents include, but are not limited to,toluene, xylene, methyl ethyl ketone, methyl isobutyl ketone, ethylacetate, butyl acetate, cyclohexanone, cyclohexanol, alcohols (e.g.,methanol, isopropanol, ethanol, etc.) and chlorinated solvents (e.g.,dichloromethane) and mixtures thereof. Any suitable polymer may beselected by one skilled in the art which is capable of functioning as amatrix for the antimicrobial agents described (and other optionalingredients) for coating specified. It is evident that depending on theparticular application or use and other pertinent considerations, anappropriate choice of polymer may readily be made.

Organic polymers may act as a carrier and matrix for the bridgedpolycyclic compounds described herein.

In some embodiments, a polymer matrix may have binding properties forthe metal precursors (e.g., core-shell bridged polycyclic compounds,metal oxide bridged polycyclic compounds, core-partial shell bridgedpolycyclic compounds) used to form a surface coating (e.g.,polyethylenimine (PEI), a substituted PEI such ascarboxylated-polyethylenimine (PEIC) or a polymer such as polyacrylicacid, polypyrolidone, and poly(ethylene-maleic acid)). Polymers mayinclude PEI or substituted PEIs such as PEIC. Typically, the molecularweight of such polymers is greater than about 30,000. Polymers such asPEI and polymer precursors of such polymers may form a matrix forbridged polycyclic compounds which cross couple the bridged polycycliccompounds to one another. PEI may be used as a matrix or medium whichassist in spreading bridged polycyclic compounds described hereinuniformly. Upon application of a PEI matrix including bridged polycycliccompounds, the composition may be alkylated polymerizing the matrix.Examples of polymer matrices with binding properties for metal oxidebased bridged polycyclic compounds include, but are not limited to,polyalkene latex and cellulosic polymer.

Admixing the bridged polycyclic compounds and an organic polymericcompound in a usual manner and then coating the mixture obtained onto asurface (forming it into films) may produce coated products withantimicrobial properties. The formation of the film may be carried outaccording to any known methods (e.g., for roll coating polymercoatings).

Specialty matrices may be used depending on what surface a coating isapplied to. For example, in some embodiments, a coating composition mayinclude pigments and used as a paint or paint equivalent. A paintequivalent may include a wet adhesion monomer containing across-linkable hydroxyl group useful in the making of latex paints.Methods for making such aqueous polyurethane-vinyl polymer dispersionmay be found in U.S. Pat. No. 6,538,143 to Pinschmidt, Jr. et al.(“Tinschmidt”), which is incorporated by reference as if fully set forthherein. In some embodiments, coating compositions described herein mayinclude specialty matrices for ink jet paper coatings. Ink jet papercoatings may be made having high optical density images, excellent waterfastness, and fast print drying times. The coating composition comprisesmay include inorganic pigments (e.g., silica), a non-polymeric polyamineand polyvinyl alcohol. High optical density images and excellent waterresistance may be achieved by incorporating amine functional emulsionpolymers in the ink jet coating formulation. Emulsion polymers mayinclude 2-(dimethylamino) ethyl methacrylate (DMAEMA), vinyl acetate,and poly(vinyl alcohol). Methods for making such aqueouspolyurethane-vinyl polymer dispersion may be found in U.S. Pat. No.6,455,134 to Rabasco (“Rabasco”) and U.S. Pat. No. 6,458,876 to Rabascoet al. (“Rabasco”), which are incorporated by reference as if fully setforth herein.

Solvents (or liquids to disperse the polymer) which may be used include,but are not limited to, aliphatic hydrocarbons, aromatic solvents,alcohols and other oxygenated solvents, substituted hydrocarbons,phenols, substituted aromatic hydrocarbons and halogenated aliphatichydrocarbons. Each resin system has a group of solvents and diluentscompatible with the resin and suitable for film forming. In some casesthe organic solvent is only used to disperse the resin powder. It iscontemplated that water may be used as solvent/diluent or dispersant forsome resin compositions.

The polymer coatings may contain other additives as well asantimicrobial compositions. They may contain, for example,polymerization catalysts, stabilizers, delustering agents, opticalwhitening agents, organic or inorganic pigments, inorganic fillers,plasticisers and so on. It is also possible that the antimicrobialparticles themselves may fulfill a dual role and provide the benefits ofsome of the aforementioned additives.

Matrices may include white pigments such as magnesium oxide, calciumoxide, aluminum oxide, zinc oxide, titanium dioxide, silicon dioxide,calcium carbonate, magnesium carbonate and barium sulfate. In addition,to the present antibacterial oxide or zeolite may be added additivessuch as magnesium silicate, aluminum silicate, zinc silicate, silicagel-zinc, synthetic hydrotalcite, aluminum tripolyphosphate.

Conventional procedures for incorporating powders in polymercompositions may be used to prepare matrices with bridged polycycliccompounds as described herein. Antimicrobial compounds may be added to amonomer or to an intermediate product prior to polymerization. In someembodiments, antimicrobial compounds may be mixed or compounded with afinished polymer before it is applied as a film. Pre-coating ofantimicrobial particles with polymers greatly facilitates incorporationof the particles in the bulk polymer. This may be done, for example, byslurring the antimicrobial compounds with a solution of the polymer,then removing the solvent by drying. From about 0.1 to about 10% byweight of polymer based on the coated antimicrobial compounds and fromabout 0.5 to about 5% by weight of polymer based on the coatedantimicrobial compounds may be suitable for this purpose.

In some embodiments, a coating is placed onto a surface wherein thecoating composition is comprised of dispersed epoxy resin particles. Theepoxy resin may be a solid or liquid epoxy resin. The epoxy resin may bea liquid that is dispersed (i.e., emulsified) within the solvent.Exemplary epoxy resins include diglycidyl ether of bisphenol A, such asthose available from The Dow Chemical Company, Midland, Mich. under thetrade name D.E.R., and from Shell Chemical Company, Houston, Tex. underthe trade name EPON or EPI-REZ and phenol and cresol epoxy novolacs,such as those available under the trade name D.E.N. from The DowChemical Company, Midland, Mich. Other examples of useful epoxy resinsinclude those described in U.S. Pat. Nos. 5,118,729, 5,344,856 and5,602,193, which are incorporated by reference as if fully set forthherein. The amount of epoxy resin in the coating composition may be anyamount sufficient to coat a surface that, subsequently, may be cured toform a microbial resistant coating on the surface.

The epoxy coating composition may also contain a surfactant that formsan epoxy resin in water dispersions, wherein the epoxy resin moleculeshave a neutral or positive surface charge, the surfactant being anonionic surfactant, amphoteric surfactant or mixture thereof. Thenonionic surfactant may be, for example, a nonionic surfactant orcombination of surfactants known to form oil in water emulsions.Exemplary nonionic surfactants include, but are not limited to,polyglycol ether of an epoxy, an alcohol, fat, oil, a fatty acid, afatty acid ester or an alkylphenol. Exemplary amphoteric surfactantsinclude, but are not limited to, those known in the art, such as alkylbetaines and dihydroxyethyl glycinates.

In some embodiments, an epoxy resin may be polymerized such that bridgedpolycyclic compounds suspended within the matrix are cross-coupled toone another and to a surface. In some embodiments, a nucleophile,specifically a dinucleophile may be employed to accomplish such an end(e.g., a diamine). Examples of epoxy resins as well as techniques forpolymerizing resins may be found in U.S. Pat. No. 5,350,814 to McGarry(“McGarry”), which is incorporated by reference as if fully set forthherein.

Examples of expoxy resins may include the butyl glycidyl ether; styreneoxide; phenyl glycidyl ether; p-butyl phenol glycidyl ether;polyglycidyl ethers of polyhydric polyols; cycloaliphatic epoxy resinsmade from epoxidation of cycloalkenes with peracids; the polyglycidylesters of aliphatic, cycloalipnatic, or aromatic polycarboxylic acids;the polyglycidyl ethers of polyphenols, (e.g., bisphenol A); and novolakresins (e.g., epoxy phenol novolak resins and epoxy cresol novolakresins); and aromatic glycidal amine resins (e.g., triglycidylderivatives of p-aminophenol).

Amine-terminated and/or ammonium-terminated flexible polymers mayinclude amine-terminated polyethers, amine-terminated diene basedpolymers, amine-terminated hydrogenated diene or polyalkene basepolymers, saturated polyesters, copolymers of vinyl substitutedaromatics and conjugated dienes, and amine-terminated copolymers ofnitrile rubber. Amine-terminated flexible polymers may include branchedpolymers. The amine termination may be one or more ends of the polymerchains. Thus, as amine reactants, they may be mono-, di- ortrifunctional, as well as, blends of mono-, di-, and trifunctionalpolymers.

Flexible epoxy resins are made by reacting uncured epoxy resin with anamine curing agent in the presence of a low molecular weight acrylatecopolymer having functional groups that may react with the epoxy resinor the amine curative. For example, acrylate copolymers are made frombutyl acrylate and acrylic acid or maleic anhydride and have numberaverage molecular weights of 1000 to 6000. The resulting flexible epoxyresins exhibit elongations up to 200%. Examples of epoxy resins, andspecifically techniques for forming flexible epoxy resins may be foundin U.S. Pat. No. 5,698,657 to Conner et al. (“Conner”), which isincorporated by reference as if fully set forth herein.

The amount of surfactant present in the coating composition may be anyamount sufficient to disperse the epoxy resin and cause the epoxy resinparticles in the dispersion to have a neutral or positive charge.Generally, the amount of surfactant is at least about 0.1 percent byweight or at least about 0.5 percent by weight. Generally, the amount ofsurfactant is at most about 10 percent or at least about 5 percent byweight of the total coating composition weight.

The epoxy coating composition may contain a latent curing agent.Examples of latent curing agents include dicyandiamide and blockedisocyanates, such as an alcohol-blocked toluene diisocyanate. The latentcuring agent is dicyandiamide. The amount of latent curing agent is anamount sufficient to cure the epoxy resin and generally should be anamount that is not so great that the coating, after curing, fails toprovide the desired properties. Generally, the amount of latent curingagent is at least about 0.1 percent by weight or at least about 0.5percent by weight. The amount of latent curing agent is at most about 10percent or at least about 5 percent by weight of the total coatingcomposition weight.

Examples of curing agents useful for curing epoxy resins may be found inU.S. Pat. No. 6,008,313 to Walker et al. (“Walker”), which isincorporated by reference as if fully set forth herein.

The aqueous epoxy coating composition contains water in an amountsufficient, for example, to provide an epoxy in water emulsion when theepoxy is a liquid. The water should also be sufficiently pure to providea water matrix that fails to cause coagulation of the particles (e.g.,epoxy or filler particles) due, for example, to impurities (e.g., ionicimpurities).

The polymer film compositions may be clear or may contain pigmentparticles or dyes. The pigment particles may include titanium dioxide,alumina or silica. Pigment particles may include titanium dioxideparticles from about 0.1 to about 10 microns in median particle size.Pigment particles may include titanium dioxide particles from about 0.2to about 5 microns in median particle size.

In some embodiments, a coating may include fillers. Fillers may impart,for example, opacity or improved wear resistance to the coatingcomposition after it has been cured. Exemplary fillers include ceramicparticles or whiskers and known surface treated metal pigments. Fillersmay include a ceramic. Ceramics may include oxides, borides, nitrides,carbides, hydroxides, carbonates, silicides, silicates and alloysthereof.

When a coating composition contains a filler, the filler is generallypresent in an amount of about 1 percent to about 50 percent by weight ofthe total coating composition weight. The amount of the filler, whenpresent, may be at least about 2 percent or at least about 5 percent.The amount of the filler, when present, may be at most about 40 percentor at most about 35 percent.

In some embodiments, a coating composition may include a cross-linkingcatalyst, for example, to increase the rate of cross-linking (i.e.,cure) of the epoxy at a temperature. Generally, the catalyst may be, forexample, a tertiary amine or imidazole. Examples of the catalyst thatmay be employed in the coating composition include 2-methylimidazole,benzyldimethylamine, dimethyl aminomethyl phenol ortris(dimethylaminomethyl)phenol.

When the coating composition contains a cross-linking catalyst, thecatalyst is generally present in an amount of about 0.001 percent toabout 1 percent by weight of the total coating composition weight. Theamount of the catalyst, when present, is at least about 0.002 percent,at least about 0.005 percent, ory at least about 0.01 percent to at mostabout 0.7 percent, at most about 0.5 percent and at most about 0.3percent by weight of the total weight of the coating composition.

In some embodiments, a coating composition may also contain a smallamount of defoamer. The defoamer may include any suitable defoamer, suchas those known in the art. Exemplary defoamers may includesiloxane-based defoamers. The defoamer, when present, is present only ina quantity necessary to control the foaming of the coating composition.It has been found that, in general, the defoamer impedes the adherenceof the coating composition to a metal surfaces. The amount of defoamer,when present, is generally present in an amount of at most about 0.15percent, at most about 0.05 percent, or at most about 0.02 percent byweight of the total weight of the coating composition.

In some embodiments, compounds or additives included in an antimicrobialcomposition may be selected to adjust particular properties of thecomposition or to introduce new properties to the composition. Adjustingproperties of a composition based on a selection of a particularcompounds or additives allows further customization of a composition. Insome embodiments, compounds or additives which have or enhanceantimicrobial properties and/or anti-inflammatory properties (e.g.,boron (e.g., boric acid), zinc) may be used. In some embodiment,compounds or additives may adjust the hydrophilicity or hydrophobicityof the complex. Research has held that specific additives do affect theantimicrobial activity of quaternary ammonium compounds in certaincoating compositions (e.g. boric acid, tetrafluoroborate counter ion,hexafluorophosphate, bis(trifluoromethanesulfonyl)imide, EDTA, disodiumEDTA). In some embodiments, before a coating composition is applied to asurface the surface may be cleaned. A degreasing operation may beperformed to promote a good adherence of the coating. If a surface isnot degreased, the fatty substances and other surface contaminants thatare not removed are liable to reduce the adherence of the resin coatingand to give rise to a nonhomogeneous deposit comprising areas withoutcoating.

In some embodiments, a surface is desirably free of contaminants, suchas petroleum greases and oils, that may cause the pretreatment andcoating to be insufficiently adhered to the surface. Prior to applyingthe coating composition a surface may be cleaned. Various methods ofcleaning are well known in the art. The particular cleaning methodshould be able to adequately remove residual oil or dirt from thesurface but should not cause over-etching of the surface, except whendesirable. Exemplary cleaning methods may include, but is not limitedto, solvent cleaning (such as a chlorinated solvent (e.g., methylenechloride), ketone (e.g., acetone), alcohol (e.g., methanol), ortoluene), emulsion cleaning, alkaline cleaning, acid cleaning, pickling,salt bath descaling ultrasonic cleaning, roughening (e.g., abrasiveblasting, barrel finishing, polishing and buffing, chemical etching andelectro-etching).

Degreasing of a surface may be generally performed either chemically orelectrolytically. A surface may be cleaned by mechanical means (e.g.,grinding or sandblasting). A surface may be degreased chemically bybeing placed in contact with a solution containing halogenated organicsolvents (e.g., methylene chloride, 1,1,1-trichloroethane,perchloroethylene, or trichloroethylene).

The degreasing operation may be performed electrolytically in anelectrolysis bath or electrolyte including an aqueous solutioncontaining alkaline mixtures similar to those just specified or elsecalcium carbonate or potassium hydroxide. The electrolyte may contain analkaline compound in a proportion of from about 0.5 to about 20 wt. %.The temperature of the electrolyte may be between from about 25° andabout 95° C. The surface may be subjected to a current density ofbetween 0.1 and 20 A/dm2 for a period longer than about 0.1 seconds.

The surface may be degreased chemically by employing a solution based onalkaline mixtures containing one or more agents including, but notlimited to, caustic soda, soda ash, alkaline silicates, sodiumhydroxide, sodium carbonate, sodium metasilicate, phosphates, alkalinebuilders, ammonium acid phosphate, ammonium hydroxide, monoethanolamine, and dimethylamine oxide and optionally containing one or more ofthe agents including, but not limited to, complexing agents,surfactants, sequestrant, builders, surface-active agents, defoamingagents, and mixtures thereof. The alkaline degreasing solutions andalkaline degreasing agents employed for cleaning metal surfaces are wellknown in the literature. Exemplary methods will use a solution ofpotassium or sodium hydroxide at a concentration of from about 1 toabout 5%. The degreasing solution is applied to the surface by knownspray or dip methods. Generally, these are applied at a temperature offrom about 50 to about 200° C. or from about 60 to about 80° C.

Alkaline builders may be generally classified into three types, namely,the strong alkaline type composed mainly of sodium silicate or trisodiumphosphate and/or caustic soda, medium alkaline type composed of one ormore than one of the following; disodium phosphate, sodiumpyrophosphate, sodium carbonate, etc., and mild alkaline type composedof disodium phosphate, sodium bicarbonate, sodium tripolyphosphate,sodium sesquicarbonate, etc. Any alkaline builder of the above types maybe employed therefore.

The temperature of the alkaline solution may be generally between about25° and about 95° C. The temperature of the alkaline solution may begreater than about 50° C. The temperature may be greater than about 60°C. A surface may be generally subjected to the solution for a periodlonger than 0.1 second. A surface may be subjected to the alkalinesolution for a period longer than 1 second. A surface may be subjectedto the alkaline solution for a period longer than 3 seconds. In general,alkaline chemistry can be deactivating towards antimicrobial ammoniumsalts. However, this can be counteracted by adjusting pH back to neutralor acidic by neutralizing the surface before adding the antimicrobialcoating. Inclusion of chelating agents such as EDTA in the antimicrobialformulation can also help avoid deactivation by magnesium, calcium orother counterions of the alkaline solution and/or painted surface beforeantimicrobial coating application. An antimicrobial coating formulationthat is acidic may also aid in neutralizing the pH of the alkalinesolution cleaned surface.

The concentration of the cleaning agent and the surfactant must besufficient to remove substantially all oil and other contaminants from asurface to be coated, but must not be so high that a significant amountof foaming occurs. Typically, the water rinse step may be avoided if thecleaning bath is not too concentrated, which is acceptable in the eventthat the surface is initially relatively clean.

A surface having been contacted by the cleaning solution may begenerally rinsed with water (neutral medium) or other known rinse agent,also by known spray or dip methods. Air-drying or other drying means maygenerally follows rinsing.

In some embodiments, a surface cleaning step may be eliminated orcombined with the surface pre-treatment step in certain circumstancesdepending upon the condition of the surface and the type ofpre-treatment utilized.

In some embodiments, a surface to which a coating composition is appliedmay be pretreated to enhance the adhesion of the coating compositionafter curing. The pretreatment may be, for example, the formation of aninterlayer on the surface that enhances adhesion of the coatingcomposition after curing. For example, the interlayer may be a chemicalconversion layer (e.g., a silane, phosphate, chromate, epoxy, or oxidecoating) or the interlayer may be an adhesive coating. Generally,pretreatment may be performed by contacting the surface with chromiumphosphate, chromium chromate, zinc phosphate, iron phosphate, or anorganic epoxy-based composition.

The interlayer may be any thickness sufficient to enhance the adhesionof the coating composition during application and after curing but, ingeneral, the interlayer is at most about 100 percent of the thickness ofthe cured coating of the antimicrobial composition on one side, theinterlayer is at most about 50 percent of the thickness of the curedcoating of the antimicrobial composition, or the interlayer is at mostabout 10 percent of the thickness of the cured coating of theantimicrobial composition. The interlayer, typically, is between about0.01 to about 30 microns thick. Thickness of the interlayer is at leastabout 0.1 microns, at least about 0.2 microns, or at least about 0.5microns. Thickness of the interlayer is at most about 20 microns, atmost about 15 microns, or at most about 10 microns.

In some embodiments, a surface may be pretreated with an aqueouscomposition including phosphoric acid and a divalent metal ion when athe surface is steel, zinc or zinc based alloys or zinc aluminum alloycoated steel, aluminum or aluminum alloy. Any divalent metal ion may beused as the divalent metal ion for use in the composition. Generally,the metal may include, but not limited to, divalent transition metalions (e.g., Mn, Co, Fe, Ni, and Zn), and alkaline earth divalent metalions (e.g., Mg, Ca, Sr, and Ba). The metal may be Fe or Zn. The metalmay be Zn. Silicate may be added to precipitate out any metal ions thatmay then be removed from the phosphating composition.

To accelerate the formation of the phosphate layer, oxidants may beadded (e.g., bromate, chlorate, nitrate, nitrite, organic nitrocompounds, perborate, persulfate or hydrogen peroxide, m-nitrobenzenesulfonate, nitrophenol or combinations thereof).

In some embodiments, to optimize the layer formation on certainmaterials, sulfate, simple or complex fluoride ions, silicofluoride,boron fluoride, citrate, tartrate, hydroxy-carboxylic acids,aminocarboxylic acids, condensed phosphates, or SiO-containing compounds(e.g., alkali metal metasilicate, alkali metal orthosilicate, and alkalimetal disilicate) and mixtures thereof may be added.

When a surface is predominantly galvanized metal and/or steel, thepretreatment may include contacting the metal surface with an aqueouscomposition comprising phosphoric acid and a divalent metal ion, thecomposition generally having a total phosphate content from about 0.01to about 3 moles/liter, a total phosphate content from about 0.02 toabout 2 moles/liter, or a total phosphate content from about 0.1 toabout 1 moles/liter. The composition may have divalent metal ion contentof from about 0.001 to about 2 moles/liter (based on metal ion content),a metal ion content of from about 0.01 to about 1 moles/liter, or ametal ion content of from about 0.05 to about 0.5 moles/liter.

In some embodiments, a surface may include an aluminum, aluminum alloy,or aluminized steel sheet, in order to enhance corrosion resistance,surface hardness and adhesive property of the substrate, an oxide film(alumite) may be formed on the sheet by pretreatment (anodizing) withcaustic soda, oxalic acid, sulfuric acid or chromic acid.

The quantities of the components in a coating composition may vary butare typically chosen to suit a particular material/substance which isprevalent in the surface being treated.

The pretreatment compositions may be prepared by the addition of thecomponents in any convenient order known to one skilled in the art.

In some embodiments, after a coating composition is applied, the coatingis at least partially cured or dried to harden and adhere the coating toa surface. The curing is by means suitable to the polymer compositionused. Curing may be accomplished using methods including, but notlimited to, heating, infrared radiation, fluorescent radiation,ultraviolet radiation, gamma or beta radiation, X-ray radiation, orcombinations thereof. In an exemplary method, a surface, immediatelyafter coating, is passed through a gas-fired heating zone where solventsare evaporated and the resin is cured or dried. The polymer may be atleast partially cured by heat. Heat curing may be employed to raise thetemperature of the coating to accelerate cross-linking reactions. Heatcuring may be accomplished by various heating means such as an electricheating oven, hot air heating oven, infrared heating oven, andhigh-frequency heating oven. For curing, a heating temperature and timeare properly selected in consideration of the formulation of a coatingcomposition, the size and composition of a surface material, thecapacity of an oven, and other factors. The particular temperature isdependent on such things as the particular epoxy, curing agent andcatalyst employed and curing time desired. The temperature, however,should not be so great that the cured coating is degraded, for example,by decomposing. Generally, the drying or curing treatment is carried outunder normal pressure or reduced pressure at a temperature of at leastabout 50° C. to at most about 400° C., depending upon the from whatmaterial the surface is formed.

The time at the temperature of cure may be any time necessary to curethe surface coating and is desirably as short as practical. Generally,the time at the curing temperature may be at least about 0.1 minute toat most about 24 hours. The time at the cure temperature may be at leastabout 10 minutes, at least about 5 minutes, or at least about 0.5minute. The time at the cure temperature may be at most about 2 hours,at most about 1 hour, or at most about 0.5 hour. As well within theknowledge of those skilled in the art, the temperature and time are in arelative relationship and also the conditions vary depending on theproperties of coating required.

Immediately after heating to cure or dry the coating, the coated surfacemay be subjected to quenching in order to harden the coating. Thequenching may be by any suitable means as known in the art such as bywater or other coolant immersion, spray, or mist or by cold air.

The thickness of the coating may be in the range of from about 0.5 toabout 30 microns. Thickness of a surface coating may be at least about 2microns, at least about 3 microns, or at least about 4 microns.Thickness of a surface coating may be at most about 20 microns, at mostabout 15 microns, or at most about 10 microns.

After curing, the applied coating composition, a surface having a curedresin coating adhered thereto is formed generally having antimicrobialproperties. In some embodiments, a coating that is formed, typically,has self-cleaning properties.

In some embodiments, bridged polycyclic compounds describes herein maybe used to form antimicrobial coatings for surfaces. Bridged polycycliccompounds may be suspended in matrices as described herein which may beused to couple the bridged polycyclic compounds to the surface and/or toeach other. In some embodiments, coating may be self-cleaning (e.g.,superhydrophobic, inhibit microbial adhesion). Antimicrobial coatingsmay be applied to any surface which would benefit any of thecustomizable properties (e.g., antimicrobial, self-cleaning) imparted bycoatings described herein. Coatings may be applied to medical devices.Medical devices may include invasive medical devices such as catheterswhich are temporarily positioned within a patient or subject. In aspecific embodiment, medical devices may include invasive dental devices(e.g., drills, suction tubes). Medical devices may include invasivedevices such as medical implants (e.g., dental implants). Medicaldevices may include non-invasive devices and systems (e.g., kits, kitpackaging, trays, medical/dental equipment, medical/dental instruments,medical containers such as blow fill seal vials and bottles forpharmaceuticals).

Surfaces to which antimicrobial coatings may be applied include, but arenot limited to, countertops, doorknobs, faucets, handles, portions ofpublic areas, etc.

Other examples of surfaces and materials to which a surface coating maybe applied are presented herein below. For example, fiberglass surfacesinclude resins, polymers, reinforcing fabric and fibers. Surfaces madefrom fiberglass include but are not limited to bathtubs, boats,motorcycles, car bodies, canoes, airplanes, model aircraft, jet skis,sculptures, as well as traditional industrial molding and model-makingarticles.

There are seven basic types of surface plastics which includepolyethylene terephthalate (PET), high density polyethylene (HDPE),polyvinyl chloride (PVC), low density polyethylene (LDPE), polypropylene(PP), polystyrene (PS), polyester, polymers and mixtures thereof. Thesetypes of plastics may also be combined with other materials including,but not limited to bridged polycyclic compounds, to make all sorts ofcomposites. Manufacturers are unlimited in the number and types ofarticles that may be made from plastic. Carbon and graphite fibers arehigh-strength materials that are used as reinforcing agents in plasticcomposites. Examples of plastic articles include vials, blow-fill-sealcontainers, bottles, jars, jugs, bags, covers, pipes, furniture,containers, caps, cups, trays, aircraft fuselages and wings, spacecraftstructures, and sports equipment.

Both ferrous and nonferrous metal surfaces are available for use withsurface coatings described herein. These include aluminum, brass,bronze, chrome, copper, tin, zinc, iron, stainless steel, and steel.Examples of metal surfaces include, but are not limited to, buildings,doors, window frames, automobiles, boats, structures, and many more toonumerous to mention.

Three basic types of glass include sheet, plate, and float. These basicglass types may be changed to meet modern requirements for comfort,security, safety, and architectural needs by adding chemicals or otheringredients during fabrication and processing.

There are a number of distinct dishware surface types available.Dishware may include glassware, ceramic ware, plastic ware, wood wareand metal ware. Examples of dishware may include agateware, basalt,bisque, bone china, cauliflower ware, cream ware, delft, earthenware,flambe, hard paste porcelain, ironstone, jackfield, jasper, lusterware,majolica, marbled, parian, pate-sur-pate, pearl ware, porcelain,redware, salt glaze, slipware, snowman-porcelain, soft paste porcelain,spatter ware, staffordshire figures, stoneware, tortoiseshell, andtransfer ware. Utensils may also be made from any of the abovematerials.

Ceramic surfaces include glazed tile, mosaic tile, and quarry tile.Applications of ceramic tiles include countertops, walls, floors,ceilings and appliances.

Other types of surfaces, such as sinks, bath tubs, towel racks, andtoilets may be made of porcelain, ceramic, or other materials. Othersurfaces may include any surface associated with a bathroom and/orkitchen area (e.g., plumbing and/or electrical fixtures).

There are many types of wood surfaces available. Examples of some typesof wood include, but are not limited to, alder, ash, aspen, beech,birch, bocote, bubinga, butternut, cedar, cherry, cocobolo, canarywood,cypress, ebony, hickory, holly, kingwood, lacewood, locust, mahogany,maple, oak, osage, parawood, padauk, pecan, persimmon, poplar,purpleheart, redheart, rosewood, spanish cedar, sycamore,. teak,tulipwood, walnut, wenge, zebrawood, ziricote. Articles made from woodmay include furniture, baseball bats, chairs, stools, furniture,handles, motor-vehicle parts, barrels and crates, sporting and athleticgoods, railroad ties, veneer, flooring, treated lumber, such as thatused for decks, siding, crates, and interior finishing.

Three basic types of stone surfaces available include igneous,metamorphic, and sedimentary. Some of these surfaces may includegranite, marble, slate, sandstone, serpentinite, schistose gneiss,quartzite, sandstone, limestone and fieldstone. Stone is often used inconstruction of buildings, roads, walls, fireplaces, and monuments.There are a number of types of concrete surfaces available as well.These surfaces may include unreinforced concrete, reinforced concrete,cast-in-place concrete, precast concrete, post-tensioned concrete, andprestressed concrete. Examples of concrete surfaces may include buildingcomponents, bridge components, walls, streets, curbs and gutters. Fourtypes of asphalt include hot-mix asphalt, cold-mix asphalt, glassphalt,and rubberized asphalt. Asphalt is used on road surfaces, walls,roofing, and sporting tracks. There are a multitude of mineral surfacesavailable. Minerals include ores of metal and other natural substancesthat may be mined. Examples of mineral surfaces may include jewelry,furniture, building components and many more. Finally coated and paintedsurfaces are also examples of hard surfaces that may be modified toderive the desired benefits.

In certain aspects, surfaces described herein are may be rigid (notflexible). Examples of surfaces that are not considered to be rigidwould include films. In certain aspects, surfaces described herein aremore rigid than a synthetic resin film having a thickness of 0.1 mm.

In some embodiments, it is desirable for the coating compositions to beapplied to exposed surfaces. As used herein, the term “exposed surfaces”includes exterior surfaces that are exposed to the elements. In someembodiments, the coating compositions are applied to interior surfacesthat are subject to periodic contact with water (including, but notlimited to the bathroom surfaces described above). Interior surfacesthat are subject to periodic active contact with water may bedistinguished from interior surfaces on which water or condensationmerely passively accumulates, based on the fact that the former may havewater showered, rinsed, or splashed thereon.

In some embodiments, surfaces described herein need not be transparent.That is, the surfaces may be translucent or opaque.

Construction Applications using Compositions Comprising Bridgedpolycyclic Compounds

Specialty matrices may be used depending on what surface a coating isapplied to. For example, in some embodiments, a coating composition mayinclude pigments and used as a paint or paint equivalent. A paintequivalent may include a wet adhesion monomer containing across-linkable hydroxyl group useful in the making of latex paints.Methods for making such aqueous polyurethane-vinyl polymer dispersionmay be found in U.S. Pat. No. 6,538,143 to Pinschmidt, Jr. et al.(“Pinschmidt”), which is incorporated by reference as if fully set forthherein.

In some embodiments, special formulations of coating may be prepared foruse in various areas of construction (e.g., architectural construction).

An antimicrobial coating composition may be prepared by paint makingtechniques which are known in the coatings art. In some embodiments, atleast one pigment is well dispersed in a waterborne medium under highshear such as is afforded by a mixer. Then an emulsion-polymerizedaddition polymer is added under low shear stirring along with othercoatings adjuvants as desired. The antimicrobial coating composition maycontain, in addition to the pigment(s) and the latex polymer,conventional coatings adjuvants such as, for example, colloids,emulsifiers, coalescing agents or solvents (e.g., DMF and ethyleneglycol), curing agents, thickeners, humectants, wetting agents,biocides, plasticizers, antifoaming agents, colorants, waxes, pHadjusters (e.g., boric acid), and antioxidants.

In particular, coalescing agents or solvents are used in architecturaland industrial latex coatings to promote film formation, and selectionof the proper coalescing solvent is a key to the formulation of superiorlatex coatings. A coalescent is often used in water-based systems as afugitive plasticizer to soften the resin particles, enabling them tofuse into a continuous film. During the drying process, most or all ofthe coalescent evaporates, allowing the film to achieve the desiredhardness. Other coalescing agents or solvents may include, but are notlimited to, dimethylsulfoxide, dimethylformamide, acetone, butanol,propanol, isopropanol, pentanol, hexanol, propylene glycol, ethyleneglycol, ethylene glycol 2-ethylhexyl ether, di(ethyleneglycol)2-ethylhexyl ether, ethylene glycol butyl ether, di(ethyleneglycol)hexyl ether, 3-ethylhexanol, hexanol, 1,4-butanediol and thelike.

In some embodiments, complexing agents (e.g., chemical compounds,polymers) may be added to a antimicrobial composition. A good example ofthis might be in a composition including pigments which will be used asan antimicrobial paint. Certain compounds (e.g., magnesium) may reducethe effectiveness of quaternary ammonium based antimicrobialcompositions, however, the addition of complexing agents which mightneutralize these compounds may overcome this problem. An example of acomplexing agent may include, but is not limited to,ethylenediaminetetraacetic acid (“EDTA”) and salts thereof (e.g.disodium EDTA).

The antimicrobial coating composition may be applied to a surface suchas, for example, metal, wood, sheet rock, ceramic, cultured marble andplastic, using conventional coating application methods such as, forexample, brush, roller, drawdown, dipping, curtain coater, and sprayingmethods such as, for example, air-assisted spray, airless spray, highvolume low pressure spray, and air-assisted electrostatic spray.

Coatings including the bridged polycyclic compounds as described hereinmay include antimicrobial paint compositions, caulk compositions,adhesive compositions and sealant compositions, and methods of preparingsuch compositions.

Coatings including the bridged polycyclic compounds as described hereinmay include a latex paint composition comprising an antimicrobial latexprepared as described herein, a pigment, and, optionally, thickener.

In some embodiments, antimicrobial compositions may take the form of acoating, adhesive, sealant or elastomer.

Coatings and Paints: Paints are typically liquids which are useful forapplication to a substrate, such as wood, metal, glass, ceramics,fiberglass, composite materials, cardboard, corrugated board, paper,textiles, non-woven materials, plastic, foam, tape or a combinationthereof, in a thin layer. Paints are typically used to protect thesurface of the substrate from elemental damage and/or physical damage.Paints are also commonly used for decoration and aesthetic purposes.Paints find very broad commercial use and also find a variety of uses inthe home. Paints, their formulations, ingredients, additives andprocessing conditions are generally described in Kirk-Othmer-Paint; pg.1049-1069, Vol. 17; 1996, by Arthur A. Leman, the disclosure of which isincorporated herein.

Typically, paints are described as latex, alkyd, or oil-based paints.Additionally, a wide variety of paints are water-based. Thesedesignations identify the binder used in the manufacture of the paintand the solvent, if any, which is used. Typically classes of latexpaints include gloss, semi-gloss, flat, and satin. These terms describethe shininess of the paint surface after the paint as dried on thesubstrate. Paints typically contain binders/resins, such as latexemulsions. A common latex emulsion employed in paints is based onacrylic and vinyl acetate. Paints often include pigments (organic andinorganic), inorganic extenders, filler pigments, solvents, andadditives, such as thickeners, protective colloids, biocides, driers,pigment dispersants, pigment extenders, adhesion promoters, surfactants,and defoamers. When paints are manufactured, surface active agents areused to stabilize the emulsion polymerization and also regulate theresulting polymer particle size.

In some embodiments, a formulation may also contain matte finishadditives (low to no gloss or flat) and thixotropic additives (anti-sagcomponents) formulations including metal oxides (e.g. silica) andsurface modified metal oxides (e.g. silica with trimethyl silyl, vinyldimethyl silyl, etc.) may be found in U.S. Pat. No. 6,720,368 which isincorporated by reference as if fully set forth herein.

The aforementioned monomers may be utilized to prepare latexes useful incoatings and paints. Typically the monomers are selected to give anacrylic latex emulsion, for durable exterior paint. These monomers mayinclude methyl methacrylate, butyl acrylate, and 2-ethylhexyl acrylate,and mixtures thereof. Non-acrylic based monomers are typically used forinterior paints, except in the cases of gloss and semi-gloss paints.Among other monomers, vinyl acetate, butyl acrylate and mixturesthereof, are commonly used in a variety of paint formulations.

Alkyd resins are produced by reaction of a polybasic acid, such asphthalic or maleic anhydride, with a polyhydric alcohol, such asglycerol, pentaerythitol, or glycol, in the presence of an oil or fattyacid.” (See Kirk-Othmer-Paint; pg. 1049-1069; Vol. 17; 1996; Arthur A.Leman). Alkyd resins are typically described as long-oil, medium-oil,and short-oil alkyds. Such description is based on the amount of oilsand/or fatty acids in the resins. Long-oil alkyds generally have an oilcontent of 60% or more; short-oil alkyds, less than 45%; and medium-oilalkyds have an oil content in between the two. The short- and medium-oilalkyds are based on semidrying and nondrying oils, whereas long-oilalkyds are based on semidrying and drying oils.

Typical pigment extenders used in paints include, for example, titaniumdioxide, calcium carbonate, talc, clay, silica, zinc oxide, feldspar,corrosion resistance extenders, mildew resistance extenders, andfilm-hardening extenders, and mixtures thereof Solvents typically usedin paints included, for example, mineral spirits, glycol ethers (e.g.ethylene glycol and propylene glycol) and the like. In addition tobinders, solvents, pigments, and extenders, many paints containadditives. Additives include, for example, thickeners, pigmentdispersants, surfactants, defoamers, biocides, mildewcides,preservatives, driers, defoamers, antiskinning agents and pH adjustingagents and mixtures thereof (e.g. acids and bases). Additional additivesinclude hydroxyethylcellulose, hydrophobically modified alkali-solubleemulsions, and hydrophobically modified ethylene oxide urethanes.

Adhesives and Sealants: Sealants have been generally described inKirk-Othmer-Sealants; pg. 650-666; Vol. 21; 1997, by Richard Palmer andJerome Kloswski, the disclosure of which is incorporated herein. Asealant is a material that is installed into a gap or joint to preventwater, wind, dirt, or other contaminants from passing through the jointor gap. Sealants, which can also be defined by how they are tested, arerated by their ability to stretch, twist, bend, and be compressed whilemaintaining their bulk properties so they do not tear apart understress. The adhesion required of a sealant is simply the strength tohold the sealant in position as it is stressed and strained. Adhesivesare used to transfer loads and are typically designed with much highertensile and shear strengths than sealants. The most important rating ofan adhesive in many applications is the determination of how much loadit can handle. Some sealants are used as adhesives and some adhesives assealants and thus arises the occasional blurring of their roles. If thematerial's primary function is the exclusion of wind, water, dirt, etc.,it is typically a sealant.

Sealants include high performance sealants, such as for example,silicones, urethanes, and polysulfides, medium performance sealants,such as for example, acrylic sealants, and low performance sealants,such as for example, butyls, putties, and caulks. The measure of thestress of a sealant at a specific strain is referred to as the modulusof elasticity, sometimes called the secant modulus. This importantsealant property describes the force exerted by a sealant as it isstressed. Because a primary function of sealants is to adhere to thesubstrates it is in contact with, the force generated by a joint openingor closing are transmitted by the sealant to the substrate-sealant bondline. A primary factor in sealant durability is its ability to resistdecay from environmental elements. For most typical applications thisincludes extremes of high and low temperature, water, oxidation, andsunlight. Other factors include weatherability and adhesion life. One ofthe more destructive elements is exposure to sunlight; specifically,ultraviolet (UV) light. All sealants are affected by weathering butthere is much difference in the effect of weathering on differentsealants. A second key factor in determining the durability of a sealantis the ability of the sealant to adhere to the substrate through itslifetime. A sealant may have excellent resistance to uv effects, but ifit has poor adhesion performance and fails adhesively, it is of littleuse.

Commercially available silicone sealants are typically one of threecuring types: moisture-reactive (curing) sealants, moisture-releasing(latex) sealants, and addition-curing sealants. The formulation ofmoisture-curing silicones includes a silicone polymer, filler, amoisture-reactive cross linker, and sometimes a catalyst. A newer classof silicone sealants are known as the silicone latex sealants. Thesesealants are silicone-in-water emulsions that cure by evaporation of theemulsifying water. The silicone latex polymer is prepared by firstemulsifying a low molecular weight silicone polymer in water and thenpolymerizing it to the desired molecular weight. Inherent to emulsionpolymerization is the ability to produce high molecular weight polymersat a low emulsion viscosity. Next, a silicone cross-linker is added witha condensation catalyst. The cross-linker, the structure of which issimilar to those described previously, must diffuse through the waterphase and into the siloxane phase where it can react with the siliconepolymer. Addition-curing silicones in general are two-part systems thatcure by the platinum-catalyzed reaction of a silicon hydride withtypically a vinyl group attached to silicon. The basis for urethanechemistry is the reaction of an isocyanate group with a componentcontaining an active hydrogen. The first step in formulating a urethanesealant is to prepare what is commonly called the prepolymer, typicallyby reaction of a hydroxy-terminated polyether with a stoichiometricamount of diisocyanate. Polysulfide sealants were the first highperformance synthetic elastomeric sealants produce in the United States.The basic polymers are mercaptan-terminated (HS—R—H), with molecularweights ranging from 1000 to ca 8000.

There are two principal classes of acrylic sealants: latex acrylics andsolvent-release acrylics. High molecular weight latex acrylic polymersare prepared by emulsion polymerization of alkyl esters of acrylic acid.Monomer, water, surfactants, and an initiator are mixed and polymerizeduntil the acrylic monomer is depleted. Two types of monomers are used tovary polymer properties. High T_(g) monomers such as methyl methacrylateand vinyl chloride improve durability and hydrophobicity, whereaspolar-functional monomers such as hydroxyethyl acrylate are used toimprove adhesion. The maximum levels of solids for the latex polymer isapproximately 60%. In typical formulations, above this point theviscosity increases rapidly and the emulsion stability is poor. Inrelatively low solids (high water) content formulations, rather severeshrinkage occurs during cure. This can introduce stress and may be oneof the reasons most latex acrylics are of lower performance and lowermovement ability. The surfactants used are of special concern to sealantformulation because they can interfere with adhesion if improperly used.One approach to solve this problem is in corporate the surfactant intothe polymer backbone during polymerization. This approach, which placesthe surfactant in an ideal location to stabilize the emulsion, does notallow the surfactant to migrate through the aqueous phase and interferewith adhesion because the surfactant is connected to the backbone (13).The emulsion polymers are compounded into sealants by adding fillers,plasticizers, freeze-thaw stabilizers, thickeners, and adhesionspromoters. As is true of the silicone sealants, the acrylic sealants areeasy to apply and clean with water.

Another class of acrylic sealants are the solvent-releasing acrylics.Acrylic monomers are polymerized in a solvent. The molecular weight ofthe polymer is lower than in the latex acrylics because of theinherently higher viscosity of the medium. However, the percentage ofsolids is approximately 80% vs the 60% common to latex acrylics. Thenatural adhesion of most of the solvent-releasing acrylics produces someof the best unprimed adhesion in the sealant industry. However, slow,continual cure generally produces large compression sets and limitstheir use to low movement application. Also, the relatively high amountsof solvent and traces of acrylic monomer in these functions limits theiruse to outdoor applications, usually in construction.

A typical one-part pigmented siliconized acrylic latex sealant willcontain acrylic latex polymer (polymer and water), and optionalingredients selected from calcium carbonate, plasticizers, mineralspirits, propylene glycol, titanium dioxide, ammonium hydroxide,preservatives, surfactants, inorganic dispersants, organic dispersants,defoamers, associative thickener, and silane adhesion promoters, andmixtures thereof.

A typical one-part clear acrylic latex sealant formulation will containacrylic latex polymer (polymer and water) and optional ingredientsselected from plasticizers, fumed silica, surfactants, amino silanes,and ammonlium hydroxides and mixtures thereof Almost all sealantscontain a mixture of a powdered filler incorporated into a viscousliquid, which results in a viscous sealant having a paste-likeconsistency.

In some embodiments formulations used as sealants and the componentsthereof (e.g., butylacrylate latex is known as AcryGen 4096D and isproduced by GenCorp Performance Chemicals [Fitchburg, Mass.] and/orlatex known as Rhoplex CS4000 and is produced by the Rohm and HaasCompany [Philadelphia, Pa.]) may be used for construction applicationsealants and surface coatings in general and can be found in Winterowd,et.al. U.S. Pat. No. 6,608,131 which is incorporated by reference as iffully set forth herein.

Adhesives have been generally described in Kirk-Othmer-Adhesives; pg.445-466; Vol. 1; 1991, by Aldophus Pocius, the disclosure of which isincorporated herein. An adhesive is a material capable of holdingtogether solid materials by means of surface attachment. Adhesion is thephysical attraction of the surface of one material for the surface ofanother. An adherend is the solid material to which the adhesive adheresand the adhesive bond or adhesive joint is the assembly made by joiningadherends together by means of an adhesive. Practical adhesion is thephysical strength of an adhesive bond. It primarily depends on theforces of the adhesive and the adherend, as well as the engineering ofthe adhesive bond. The interphase is the volume of materials in whichthe properties of one substance gradually change into the properties ofanother. The interphase is useful for describing the properties of anadhesive bonds. The interface, contained within the interphase, is theplane of contact between the surface of one material and the surface ofanother. Except in certain special cases, the interface is imaginary. Itis useful in describing surface energetics.

Adhesive properties are often tested using various peel tests. In thesimplest peel test, the T-peel test, the adherends are identical insize, shape, and thickness. Adherends are attached at their ends to atensile testing machine and then separated in a “T” fashion. Thetemperature of the test, was well as the rate of adherend separation, isspecified. The force required to open the adhesive bond is measured andthe results are reported in terms of newtons per meter (pounds per inch,ppi). There are many other peel test configurations, each dependent uponthe adhesive application. Such tests are well described in the ASTMliterature.

A structural adhesive is a resin system, usually a thermoset, that isused to bond high strength materials in such a way that the bonded jointis able to bear a load in excess of 6.9 MPa (1,000 psi) at roomtemperature. Structural adhesives are the strongest form of adhesive andare meant to hold loads permanently. They exist in a number of forms.The most common form is the two-part adhesive, widely available as aconsumer product. The next most familiar is that which is obtained as aroom temperature curing liquid. Less common are primer-liquid adhesivecombinations which cure at room temperature.

A pressure-sensitive adhesive, a material which adheres with no morethan applied finger pressure, is aggressively and permanently tacky. Itrequires no activation other than the finger pressure, exerts a strongholding force, and should be removable from a smooth surface withoutleaving a residue. Pressure-sensitive adhesives are most widely used inthe form of adhesive tapes. These tapes are used for an extraordinarynumber of applications: masking, medical application, electricalinsulation, assembly, packaging, and other application. The applicationgoverns the choice of tape backing and the adhesive formulation. Atransparent backing having relatively weak adhesive is used for papermending; a filament filled backing having an aggressive adhesive is usedfor packaging applications. Pressure-sensitive adhesives are alsoobtainable in aerosol form for use in various graphics.

The general formula for a pressure-sensitive adhesive includeselastomeric polymer, a tackifying resin, any necessary fillers, variousantioxidants and stabilizers, if needed, and cross-linking agents. Informulating a pressure-sensitive adhesive, a balance of three physicalproperties needs to be taken into account: sheer strength, peelstrength, and tack. The shear strength or shear holding power of theadhesive is typically measured by hanging a weight on the end of a pieceof tape and measuring the time of failure. Tack is the technical termapplied to quantify the sticky feel of the material. in general, theshear strength and the tack of a pressure-sensitive adhesive increaseand then go through a maximum as a function of the amount of tackifyingresin added. The peel strength usually increases with the amount oftackifying resin. The shear holding power often depends upon the mode ofcross-linking. This, a balance of properties appropriate to theapplication is obtained by controlling the rubber-to-resin ratio as wellas the level and type of cross-linking agent.

The most widely used emulsion-based adhesives is that based uponpoly(vinyl acetate)-poly(vinyl alcohol) copolymers formed byfree-radical polymerization in an emulsion system. Poly(vinyl alcohol)is typically formed by hydrolysis of the poly(vinyl acetate). Theproperties of the emulsion are derived from the polymer employed in thepolymerization as well as from the system used to emulsify the polymerin water. The emulsion is stabilized by a combination of a surfactantplus a colloid protection system. The protective colloids are similar tothose used in paint to stabilize latex. For poly(vinyl acetate), theprotective colloids are isolated from natural gums and cellulosic resins(carboxymethylcellouse or hydroxyethylcellous). The hydrolyzed polymermay also be used. The physical properties of the poly(vinylacetate)polymer can be modified by changing the co-monomer used inpolymerization. Any material which is free-radically active andparticipates in an emulsion polymerization may be employed. Plasticizers(qv), tackifiers, humectants, and other materials are often added to theadhesive to meet specifications for the intended application. Becausethe presence of foam in the bond line could decrease performance of theadhesion joint, agents that control the amount of air entrapped in anadhesive bond must be added. Biocides are also necessary: many of thematerials that are used to stabilize poly(vinyl acetate) emulsions arenatural products. Poly(vinyl acetate) adhesives known as “white glue” or“carpenter's glue” are available under a number of different tradenames. Application are found mostly in the are of adhesion to paper andwood.

Elastomers: Elastomers have been generally described inKirk-Othmer-Elastomers; pg. 905-1079; Vol. 8; 1993; andKirk-Othmer-Elastomers; pg. 1-31; Vol. 9; 1994, by various authors, thedisclosure of which is incorporated herein. The term elastomer is themodern word to describe a material that exhibits rubbery properties,i.e., that can recover most of its original dimensions after extensionof compression. Once key class of elastomers is rubber materials.“Rubber materials, e.g., natural, SBR, or polybutadiene, beingunsaturated hydrocarbons, are subjected to sulfur vulcanization, andthis process requires certain ingredients in the rubber compound,besides the sulfur, e.g., accelerator, zinc oxide, and stearic acid.Accelerators are catalysts that accelerate the cross-linking reaction sothat reaction time drops from many hours to perhaps 20-30 min. at about130° C. In addition to the ingredients that play a role in the actualvulcanization process, there are other components that make up a typicalrubber compound.

Softeners and extenders, generally inexpensive petroleum oils, help inthe mastication and mixing of the compound. Antioxidants are necessarybecause the unsaturated rubbers can degrade rapidly unless protectedfrom atmospheric oxygen. They are generally organic compounds of theamine or phenol type. Reinforcing fillers, e.g. carbon black or silica,can help enormously in strengthening the rubber against rapture orabrasion. Nonreinforcing fillers, e.g., clay or chalk, are used only asextenders and stiffeners to reduce cost.

For Styrene-Butadiene Rubber (SBR), the polymerization is carried out inan emulsion system where a mixture of the two monomers is mixed with asoap [or other surface active agent] solution containing the necessarycatalysts (initiators). The final product is an emulsion of thecopolymer, i.e., a fluid latex.

In some embodiments, elements used within an antimicrobial coatings asdescribed herein is association with other applications or elsewhereherein (e.g., under the “Matrices” heading) may also be incorporatedinto a composition for architectural construction purposes includingcommercial and residential.

In some embodiments, an antimicrobial coating may be especially usefulin the construction of a medical, medical research facility, or nursinghome.

Marine Applications using Compositions Comprising Bridged PolycyclicCompounds

Embodiments described herein relate to coating compositions, to the useof such compositions in forming protective coatings on substrates, andto substrates bearing such coatings. Embodiments described herein relatemore especially to the protection of substrates in aquatic environments,especially marine environments, and is concerned in particular with theprovision of non-fouling protective coatings.

In some embodiments, non-fouling protective coatings may includeantimicrobial coatings.

Man-made structures such as boat hulls, buoys, drilling platforms, oilproduction rigs, piers and pipes which are immersed in water are proneto fouling by aquatic organisms such as green and brown algae,barnacles, mussels and the like. Such structures are commonly of metal,but may also comprise other structural materials such as concrete, wood,synthetic materials, etc. This fouling is a nuisance on boat hulls,because it increases the frictional resistance towards movement throughthe water, with the consequence of reduced speeds and increased fuelcosts. It is a nuisance on static structures such as the legs ofdrilling platforms and oil production rigs, firstly because theresistance of thick layers of fouling to waves and currents can causeunpredictable and potentially dangerous stresses in the structure, and,secondly, because fouling makes it difficult to inspect the structurefor defects such as stress cracking and corrosion. It is a nuisance inpipes such as cooling water intakes and outlets, because the effectivecross-sectional area is reduced by fouling, with the consequence ofreduced flow rates. Fowling is a nuisance issue as relates to forexample tools used in the water, for example nets or fishing rods,especially these items which are left at least partially submerged forlong periods of time.

The commercially most successful methods of inhibiting fouling haveinvolved the use of anti-fouling coatings containing substances toxic toaquatic life, for example tributyltin chloride or cuprous oxide. Suchcoatings, however, are being regarded with increasing disfavour becauseof the damaging effects such toxins can have if released into theaquatic environment. There is accordingly a need for non-foulingcoatings which do not contain markedly toxic materials.

In some embodiments, antimicrobial coatings may inhibit the growth of avariety of organisms. Organisms which may be inhibited by antimicrobialcoatings include, but are not limited to:

Fungi: Aspergillus flavus, A. fumigalus, A. niger, Blastomycesdermatitidis, Candidas pp., Coccidioides immitis, Cryptococcusneoformans, Fusarium culmorum, Geotrichum spp., Histoplasma capsulatum,Malassezia furfur, Microsporum spp., Mucor racemosus, Nocardia spp.,Paracoccidioides brasiliensis, Penicillium spp., Rhizopus higricans,Saccharomyces cerevisiae, Sporothrix schneckii, Torulopsis spp.,Trichophyton spp;

Bacteria: Aerobacter aerongenes, Aeromonas hydrophila, Bacillus cereus,Bacillus subtilis, Bordetella pertussis, Borrelia burgdorferi,Campylobacter fetus, C. jejuni, Corynebacterium diphtheriae, C. bovis,Desulfovibrio desulfurica, Escherichia coli 0157:H7, Enteropathogenic E.coli, Enterotoxin-producing E. coli, Helicobacter pylori, Klebsiellapneumoniae, Legionella pneumophila, Leptospira interrogans,Mycobacterium tuberculosis, M. bovis, Neisseria gonorrhoeae, N.meningitidis, Proteus mirabilis, P. vulgaris, Pseudomonas aeruginosa,Rhodococcus equi, Salmonella choleraesuis, S. enteridis, S. typhimurlum,S. typhosa, Shigella sonnei, S. dysenteriae, Staphylococcus aureus, S.epidermidis, Streptococcus anginosus, S. mutans, Vibrio cholerae,Yersinia pestis, Y. pseudotuberculosis, Actinomycetes, Stretomycesreubrireticuli, Streptoverticillium reticulum, Thermoactinomycesvulgaris;

Viruses: Adenoviruses, Coronaviruses, Cytomegalovirus, Enteroviruses,Epstein-Barr virus, Herpes simplex virus, Hepatitis viruses, HumanImmunodeficiency virus, Human Parvoviruses, Influenza viruses,Morbillivirus, Mumps virus, Norwalk viruses, Papillomaviruses,Paromyxovirus, Poxvirus, Rabies virus, Reoviruses, Rotaviruses, Rubellavirus, Respiratory Synctial virus, Rhinoviruses, Varicella zoster virus;

Parasites: Ancyclostoma braziliense, Anisakis, Babesia microti,Balantidum coli, Blastocystis hominis, Chilomastix mesnili,Cryptosporidium parvum, Cyclospora, Dientamoeba fragilis,Diphyllobothrium latum, Echinococcus granulosus, Entamoeba coli, E.histolytica, Enterocytozoon, Fasciola hepatica, Giardia lamblia,lodamoeba butschlii, Isospora belli, Leishmania brasiliensis, L.donovani, L. tropica, Paragonimus westermani, Plasmodium vivax,Pnemocystis carinii, Sarcocytis hominis, Strongyloides stercoralis,Taenia solium, Toxoplasma gondii, Trichomonas vaginalis, Trichinellaspiralis, Trypanosoma cruzi; and

Mollusks: mussels, clams, oysters, shellfish snails, bivalves, chitons,barnacles.

In some embodiments, elements used within an antimicrobial coatings asdescribed herein is association with other applications or elsewhereherein (e.g., under the “Matrices” heading) may also be incorporatedinto a composition for marine applications for anti-fouling purposes.

Dental Compositions and Varnishes Comprising Bridged polycyclicCompounds

In prospering industrial societies, life expectancy steadily increases.At the same time, a drop in birth rate is observed. Both factors resultin a change in age distribution characterized by a high proportion ofelderly people.

In the field of dentistry, the increased average age of patients alongwith achievements regarding caries prophylaxis and treatment result inan increased average age of teeth which have to be cared for.

The prevention of caries and periodontitis can therefore not be limitedto children and adolescents as the lifelong conservation of teethdemands a preventive approach also for middle-aged and elderly patients.Otherwise there is the risk that the positive results of earlypreventive measures will be lost within a few years ending up with toothloss at old age.

Dental applications are challenging and require top performance fromdental care providers and materials technology. Materials used in theseapplications need to be comfortable, hard, wear resistant, strong andyet also visibly appealing. Poorly formulated dental materials canresult in discomfort, complications, and increased health care cost toconsumers.

Demanding requirements such as those for dental materials also exist innumerous other products such as coatings. Recent developments innanotechnology are increasingly being considered to address theserequirements. A key challenge to widespread adoption of nanotechnologyto such applications is the ability to manufacture non-agglomerateddiscrete nanoparticles that can be homogeneously distributed in resinsor coatings to produce nanocomposites.

In some embodiments, a dental composition may include bridged polycycliccompounds. At least one of the bridged polycyclic compounds may includeat least two cyclic groups. At least two of the cyclic groups mayinclude quaternary ammonium or amine moieties. In some embodiments atleast two of the cyclic groups may be defined at least in part byquaternary ammonium moieties.

In some embodiments, a composition may be applied to an oral surface orat least to a portion of an oral surface. An oral surface may include atleast a portion of a dental fixture.

A method may include applying a dental composition to dental fixturesuch as bridges, caps, retainers, dentures and any temporary orpermanent dental fixture in the oral cavity.

In some embodiments, a dental composition may include core-shellnanoparticles as described herein.

In some embodiments, a dental composition may include nanoparticles asdescribed herein.

A dental composition and method of use of the same may be used inrestoring the function and anatomy of a tooth. Dental compositions asdescribed herein may be used in bonding agents, resin cements, sealants,varnishes, gels and resins. Dental compositions may includepolymerizable unsaturated monomers, oligomers, prepolymers, orcombinations thereof. Dental compositions may inhibit tooth decay and/ormicrobial growth in and around an oral cavity. Dental compositions mayinhibit secondary decay.

Some commonly found bacteria leading to tooth decay have been known forsome time (e.g. Actinomyces israelii, A viscosus, A naeslundii, Arachniapropionica, Rothia dentocariosa, Bacterionema matruchotii, andCorynebacterium acnes) as described by J. M Slack, et.al. in J. Dent.Res 50(1): 78-82, 1971, incorporated by reference as if set forth fullyherein.

In some embodiments, dental compositions may enhance sustainedantimicrobial activity with minimum harm to the living structure andsurrounding tissues and without affecting the composition's restorativeproperties.

In some embodiments, dental compositions described herein may be usedfor oral trauma treatment. Dental composition may be used for oraltrauma treatment field kits used for the temporary or permanenttreatment of oral trauma out in the field when specialized help is notreadily available (e.g., for a member of the armed services duringmaneuvers or times of war). Dental compositions may be used incombination with gelators, absorbents, and/or coagulating agents toprepare oral antimicrobial wound dressings.

Nanoparticles have been shown to enable nearly 50% reduction in fillingshrinkage. These nanocomposites are suggested to be particularly usefulfor fabricating load bearing and cosmetic restorations. Examples ofnanoparticles and general properties which they impart to dentalcompositions may be found in U.S. Pat. No. 6,593,395, which isincorporated by reference as if fully set forth herein.

A dental composite may have a high strength required for load-bearingrestorations, yet maintains a glossy appearance, even after substantialwear. Through the use of particles having a mean particle size betweenabout 0.05 .mu.m and about 0.50 micromolar, the composite is useful instress bearing restorations and in cosmetic restorations. The structuralfiller used is typically ground to a mean particle size of less than 0.5micromolar and also includes a nanofiller having discrete particles of amean particle size less than 100 nm to improve handling and mechanicalcharacteristics. The preferred dental composites maintain their surfacefinish even after substantial use and also have the strength propertiesof hybrid composite resins.

In some embodiments, a dental composite, comprising: a polymerizableresin base; and about 10% by volume to about 80% by volume fillerconsisting essentially of a ground structural filler and a non-groundnanofiller, wherein the ground structural filler comprises between about10% by volume and about 70% by volume of the composite and consists ofground particles of mean particle size between about 0.05 .mu.m andabout 0.50 .mu.m, and wherein the ground structural filler contains lessthan 50% by volume of particles above 0.5 .mu.m in diameter, and whereinthe non-ground nanofiller comprises between about 1.0% by volume andabout 15% by volume of the composite and consists essentially ofdiscrete, non-aggregated gamma alumina particles having a mean particlesize of about 40 nm or less.

The resin composite, in the cured form, may have a flexural strength ofat least 100 MPa.

The resin composite, in the cured form, may have a flexural strength ofat least 120 MPa.

The resin base comprises a polymerizable vinyl compound.

The the ground structural filler contains less than 10% by volume ofparticles above 0.8 .mu.m in diameter.

The the non-ground nanofiller comprises between about 5 and about 12% byvolume of the composite.

The dental composite of claim 1, wherein the non-ground nanofiller has arefractive index in the range of about 1.48 to about 1.6.

A dental composite comprising: a polymerizable resin base; and about 11%by volume to about 80% by volume filler in the resin base, the fillerconsisting essentially of a ground structural filler and a non-groundnanofiller, wherein the ground structural filler comprises between about10% by volume and about 70% by volume of the composite and consists ofground particles having a mean particle size of between about 0.05 .mu.mand about 0.50 .mu.m, and wherein the non-ground nanofiller comprisesbetween about 1.0% by volume and about 15% by volume of the compositeand consists essentially of discrete, non-aggregated aluminosilicateparticles having a mean particle size of less than about 100 nm, and a1:4 molar ratio of alumina to silica.

The resin composite, in the cured form, has a flexural strength of about120 MPa or greater.

The resin base includes a polymerizable vinyl compound.

The non-ground nanofiller comprises between about 5% by volume to about12% by volume of the composite.

The aluminosilicate particles have a mean particle size of about 80 nm.

The resin composite, in the cured form, has a flexural strength of atleast 100 MPa.

The ground structural filler contains less than 10% by volume ofparticles above 0.8 .mu.m in diameter.

The non-ground nanofiller has a refractive index in the range of about1.48 to about 1.6.

A dental composition may include a polymerizable compound, apolymerization initiator system, bridged polycyclic compounds, orcombinations thereof. These compositions may be suitable for restoringthe functionality and anatomy of a damaged tooth. Uses may include, butare not limited to, use as dental primers, adhesives, surface sealants,liners, luting cements, varnishes, impression materials, equipment andimpression systems, and composite restoratives. Uses may include, butare not limited to, impression materials, coatings for impression trays,and impression systems. In some embodiments, dental compositions mayimpart antimicrobial activity to a contacted tooth structure and/orsurrounding tissue.

The present dental compositions may include a polymerizable compound(e.g., at least one polymerizable monomer or prepolymer selected fromthose known in the art of dental materials) including, but not limitedto, polymerizable amides, esters, alkenes, imides, acrylates,methacrylates, urethanes, vinyl esters or epoxy-based materials. Otherpolymerizable compounds may include those based on styrene, styreneacrylonitrilic, sulfones, acetals, carbonates, phenylene ethers,phenylene sulfides, or other polymerizable units listed herein. Examplesof dental compositions and additives typically used may be found in U.S.Pat. No. 6,326,417, which is incorporated by reference as if fully setforth herein. Examples of dental compositions and additives typicallyused may be found in U.S. Pat. and patent application Ser. Nos. U.s.Pat. Nos. 6,500,004; 6,326,417; 20010009931; 20050252413; and20030134933 (acidic based sealants) which are incorporated by referenceas if fully set forth herein.

Polymerizable compounds may include ethylenically unsaturated monomersand prepolymers and include those based on acrylic and methacrylicmonomers, for example those disclosed in U.S. Pat. Nos. 3,066,112,3,179,623, and 3,194,784 to Bowen; U.S. Pat. Nos. 3,751,399 and3,926,906 to Lee et al.; and commonly assigned U.S. Pat. No. 5,276,068to Wakline, which are incorporated by reference as if fully set forthherein. Methacrylate-based monomers may be used (e.g., condensationproduct of bisphenol A and glycidyl methacrylate, 2,2′-bis[4-(3-methacryloxy-2-hydroxy propoxy)-phenyl]-propane (“BIS-GMA”),dipentaerythritol pentaacrylate (DPEPA), pentaerythritol dimethacrylate(PEDM), the condensation product of ethoxylated bisphenol A and glycidylmethacrylate (“EBPA-DMA”), and the condensation product of 2 partshydroxymethylmethacrylate and 1 part triethylene glycolbis(chloroformate) (“PCDMA”)). Polymerizable compounds may includepolyurethane-based dimethacrylates (“PUDMA”).

Polymerizable compounds may include polymerizable diluent monomers. Suchmonomers are generally used to adjust the viscosity of a polymerizablecomposition. Suitable methacrylate-based diluent monomers may include,but are not limited to, hydroxyalkyl methacrylates (e.g., 2-hydroxyethylmethacrylate, 1,6-hexanediol dimethacrylate, and 2-hydroxypropylmethacrylate); glyceryl dimethacrylate; and ethyleneglycol methacrylates(e.g., ethyleneglycol methacrylate, diethyleneglycol methacrylate,triethyleneglycol methacrylate, Triethyleneglycol dimethacrylate, andtetraethyleneglycol methacrylate).

When used as primers, adhesives, or primer/adhesive, dental compositionsmay include a polymerizable compound including hydrophilic polymerizablemonomers to enhance the bonding characteristics of the dentalcomposition. Suitable polymerizable hydrophilic monomers may havecarboxyl, phosphoryl, sulfonyl, and/or hydroxyl functional groups.Examples of polymerizable hydrophilic monomers having at least onecarboxyl group may include, but are not limited to, methacrylic acid,maleic acid p-vinylbenzoic acid,11-methacryloyloxy-1,1-undecanedicarboxylic acid,1,4-dimethacryloyloxyethylpyromellitic acid,6-methacryloyloxyethylnaphthalene-1,2,6-tricarboxylic acid,4-methacryloyloxymethyltrimellitic acid and the anhydride thereof,4-methacryloyloxyethyltrimellitic acid (“4-MET”) and an anhydridethereof (“4-META”), 4-(2-hydroxy-3-methacryloyloxy)butyltrimellitic acidand an anhydride thereof, 2,3-bis(3,4-dicarboxybenzoyloxy)propylmethacrylate, methacryloyloxytyrosine, N-methacryloyloxytyrosine,N-methacryloyloxyphenylalanine, methacryloyl-p-aminobenzoic acid, anadduct of 2-hydroxyethyl methacrylate with pyromellitic dianhydride(PMDM), and an adduct of 2-hydroxyethyl methacrylate with3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) or3,3′,4,4′-biphenyltetracarboxylic dianhydride. Hydrophilic monomers mayinclude BPDM, the reaction product of an aromatic dianhydride with anexcess of 2-HEMA (2-hydroxyethyl methacrylate), as disclosed in U.S.Pat. No. 5,348,988, which are incorporated by reference as if fully setforth herein. Other hydrophilic monomers may include EDMT, the reactionproduct of 2-hydroxyethyl methacrylate (“2-HEMA”) with ethylene glycolbistrimellitate dianhydride; DSDM, the reaction product of3,3′,4,4′-diphenylsulfone tetracarboxylic dianhydride and 2-HEMA; PMDM,and PMGDM, the adduct of pyromellitic dianhydride with glyceroldimethacrylate.

Examples of polymerizable compounds having at least one phosphoric acidgroup may include, but are not limited to 2-methacryloyloxyethylacidophosphate, 2-methacryloyloxypropyl acidophosphate,4-methacryloyloxybutyl acidophosphate, 8-methacryloyloxyoctylacidophosphate, 10-methacryloyloxydecyl acidophosphate,bis(2-methacryloyloxyethyl)acidophosphate, and 2methacryloyloxyethylphenyl acidophosphate. The phosphoric acid group inthese compounds may be replaced with a thiophosphoric acid group.Examples of polymerizable compounds may include2-methacryloyloxyethylphenyl acidophosphate and 10-methacryloyloxydecylacidophosphate. Examples of polymerizable monomers having at least onesulfonic acid group include 2-sulfoethyl methacrylate, 3-sulfo-2-butylmethacrylate, 3-bromo-2-sulfo-2-propyl methacrylate,3-methoxy-1-sulfo-2-propyl methacrylate, and 1,1-dimethyl-2-sulfoethylmethacrylamide.

All the above polymerizable monomers may be used alone or incombination.

A dental composition may include a polymerization initiator system,including light curing, self-curing, dual curing, and vacuum, heat, andpressure curing systems as well as any combination thereof. Visiblelight curing systems employ light-sensitive compounds (e.g., benzildiketones and DL-camphorquinone) in amounts ranging from about 0.05 to0.5 weight percent. Visible light curing systems may includepolymerization accelerators (e.g., various organic tertiary amines wellknown in the art). In visible light curable compositions, the tertiaryamines are generally acrylate derivatives such as dimethylaminoethylmethacrylate and, particularly, diethylaminoethyl methacrylate (“DEAME”)in amounts in the range from about 0.05 to 0.5 weight percent.

Self-curing compositions may contain free radical polymerizationinitiators such as, for example, peroxides in amounts ranging from about2 to 6 weight percent. Suitable free radical initiators may includelauryl peroxide, tributyl hydroperoxide, cumene hydroperoxide, andbenzoyl peroxide. The heat and pressure curable systems also includeheat cure initiators such as aromatic sulfinic acids and salts thereof,benzoyl peroxide, 1,1′-azobis (cyclohexanecarbonitrile), or other freeradical initiators. Polymerization accelerators commonly used with theseinclude tertiary amines, generally aromatic tertiary amines such asethyl 4-(N,N-dimethyl)aminobenzoate (“EDAB”), dimethyl-p-toluidine,dihydroxyethyl-p-toluidine and the like, in amounts ranging from about0.05 to about 4.0 weight percent.

The dental restorative compositions may also comprise other additivesand solvents known in the art, for example, ultraviolet light absorbers,anti-oxidants such as BHT, stabilizers, fillers, pigments, opacifiers,handling agents, and others. An ultraviolet absorber may be employed inamounts ranging from about 0.05 to about 5.0 weight percent. Suchultraviolet absorbers may be desirable in the visible light curablecompositions in order to avoid discoloration of the resin from anyincident ultraviolet light. Suitable ultraviolet absorbers may includegelators, various benzophenones, particularly UV-9 and UV-5411 availablefrom American Cyanamid Company, and benzotriazoles known in the art,particularly 2-(2′-hydroxy-5′-methylphenyl)-benzotriazole, sold underthe trademark TINUVIN P by Ciba-Geigy Corporation, Ardsley, N.Y.

Fillers, such as colloidal silica, barium glasses, fibrous fillers,quartz, ceramic fillers and the like may also be incorporated intodental compositions, particularly when they are to be used as bondingagents, luting cements or filling composites. Suitable fillers mayinclude fillers conventionally used in the dental industry capable ofbeing covalently bonded to the resin matrix itself or to a couplingagent which is covalently bonded to both. Silane coupling agents areknown, for example methacryloxypropyl trimethoxy silane. Such fillersare described in U.S. Pat. Nos. 4,544,359 and 4,547,531, which isincorporated by reference as if fully set forth herein. Examples ofsuitable filling materials may include, but are not limited to,amorphous silica, spherical silica, colloidal silica, barium glasses,quartz, ceramic fillers, silicate glass, hydroxyapatite, calciumcarbonate, fluoroaluminosilicate, barium sulfate, quartz, bariumsilicate, strontium silicate, barium borosilicate, bariumboroaluminosilicate, strontium borosilicate, strontiumboroaluminosilicate, glass fibers, lithium silicate, ammoniated calciumphosphate, deammoniated calcium phosphate, alumina, zirconia, tin oxide,polymer powders, polymethyl methacrylate, polystyrene, and polyvinylchloride, titania, and combinations thereof. Particularly suitablefillers for dental filling-type materials prepared are those having aparticle size in the range from about 0.1 to about 5.0 microns, togetherwith a silicate colloid having particle sizes in the range from about0.001 to about 0.07 microns.

Antimicrobials may be generally effective against organisms which causesecondary decay, and must not adversely affect the required physicalproperties of the cured compositions, in particular water sorption,diametral tensile strength, and hardness. In particular, the ADAspecification No. 27 requires dental resin composites to have watersorption values below 50 μg/mn³/week. Commercial dental restorativematerials used as, filling materials preferably have water sorptionvalues of less than about 30, less than about 20, or less than about 15μg/mm³/week. The ADA specification No. 27 specifies that the diametraltensile strength for filled dental composite (type II) should be aminimum of 34 MPa. Commercial dental restorative materials used asfilling materials may have DTS values of greater than about 38, greaterthan about 40, or greater than about 45 MPa. Dentine bonding strengthmust be at least about 10 MPa, at least about 15 MPa, at least about 18MPA, or at least about 20 MPa.

Dental compositions may be used as bonding primers or adhesives. Whendental compositions are to be used as bonding primers, adhesives, orprimer/adhesives, volatile solvents such as water, alcohol, acetone, andthe like are used to dilute the polymerizable compound(s). Theparticular amounts of polymerizable compound(s) and solvent may beadjusted so as to provide sufficient viscosity such that they can beapplied in one or a relatively few number of coats and achieve a uniformthin coating, of the dental substrate, while providing high bondingstrengths between the dental substrate and the restorative material ordental component. Optionally, additional polymerizable compounds,optional self-life stabilizers, or other modifying ingredients known inthe art may be incorporated.

Dental compositions may be used as a bonding agent and/or base linerunder restorative materials such as resin composites, silver amalgamalloys, and the like.

The most common ailments seen by vets in dogs and cats are dentalproblems. More than half of all pets suffer from gum disease, dentalcalculus or similar dental problems.

Calculus is the brown build-up of plaque found extending downwards onthe tooth from the gum line. Calculus is a haven for bacteria which canhave serious consequences for your pet's general health. These bacteriacan not only cause abscesses and tooth loss but can have effects furtherafield—even resulting in organ damage as the bacteria are carried fromthe mouth, through the bloodstream.

All types of teeth and gum diseases can lead to serious health problemsin pets. Dogs and cats make much fuller use of their teeth than humansdo—using them in ways humans usually use their hands. For this reason,toothache, dental disease and loss of teeth can all have seriousconsequences for pets. Damage to the teeth and gums in pets is permanentand irreversible.

In some embodiments this antimicrobial may be incorporated into petdental systems for plaque prevention (e.g. OraVet™ a clinically providedplaque prevention system [Merial, Duluth, Ga.]). A system featuring adental barrier sealant and a plaque prevention gel that cansignificantly reduces the formation of plaque and calculus, two factorsin the onset of periodontal disease.

Dental compositions may be used as dental luting cements and/or cavityfilling materials.

In some embodiments, elements used within an antimicrobial coatings asdescribed herein is association with other applications or elsewhereherein (e.g., under the “Matrices” heading) may also be incorporatedinto a composition for dental purposes.

Medical Device Applications using Compositions Comprising Bridgedpolycyclic Compounds

Medical devices used for patient treatment can be a source of microbial(bacterial or fungal) infection in such patients. For example, insertionor implantation of a catheter into a patient can introduce microbesand/or, when left in place for prolonged periods of time, permit theintroduction of microbes during long-term exposure of the catheter exitsite to the environment. In addition, long-term catheter use oftenproduces a biofilm on the catheter surface, which facilitates thedevelopment of infection that can cause patient discomfort andcompromise patient health.

Medical devices are any article that contacts patients or are used inhealth care, and may be for use either internally or externally. Themedical devices can be made from a variety of natural or syntheticmaterials, such as, for example, latex, polystyrene, polyester,polyvinylchloride, polyurethane, ABS polymers, polyamide, polyimide,polycarbonate, polyacrylates, polyethylene, polypropylene, syntheticrubber, stainless steel, ceramics such as aluminum oxide and glass, andsilicone.

Illustrative, non-limiting, examples include of medical devices include,but are not limited to, cannulae, catheters, condoms, contact lenses,endotracheal and gastroenteric feeding tubes as well as other tubes,grafts, guide wires, implant devices, IUDs, medical gloves, oxygenatorand kidney membranes, pacemaker leads, peristaltic pump chambers,shunts, stents and sutures Other non-limiting examples of medicaldevices include peripherally insertable central venous catheters,dialysis catheters, long term tunneled central venous catheters, longterm non-tunneled central venous catheters, peripheral venous catheters,short-term central venous catheters, arterial catheters, pulmonaryartery Swan-Ganz catheters, urinary catheters, artificial urinarysphincters, long term urinary devices, urinary dilators, urinary stents,other urinary devices, tissue bonding urinary devices, penileprostheses, vascular grafts, vascular catheter ports, vascular dilators,extravascular dilators, vascular stents, extravascular stents, wounddrain tubes, hydrocephalus shunts, ventricular catheters, peritonealcatheters, pacemaker systems, small or temporary joint replacements,heart valves, cardiac assist devices and the like and bone prosthesis,joint prosthesis and dental prosthesis.

In some embodiments, antimicrobial compositions useful for forming acoating may be supplied in the form of a kit comprising the compositionsto coat various medical devices (e.g., catheters) prior to use. Thesekits may be readily prepared by utilizing standard preparations ofantimicrobial solutions, which are readily known and applied in the art.The compositions used in the kit may be in the following forms, but arenot limited to these forms, creams, capsules, gels, pastes, powders,liquids and particles.

It is also contemplated that a kit may comprise a medical device thathas been pre-coated with an antimicrobial agent and compositions to coatthe medical device prior to implantation into a mammal. Thus, themedical staff only needs to apply the antimicrobial composition to themedical device prior to implantation. One realizes that a kit containinga pre-coated medical device will reduce the amount of time that isneeded for the implantation.

A further embodiment is a kit comprising compositions to coat thesurfaces of medical devices prior to implantation into a mammalcomprising an antimicrobial composition as described in variousemodiments herein.

In some embodiments, elements used within an antimicrobial coatings asdescribed herein is association with other applications or elsewhereherein (e.g., under the “Matrices” heading) may also be incorporatedinto a composition for medical device coatings.

Personal Care Applications using Compositions Comprising Bridgedpolycyclic Compounds

In October 2000, the first known outbreak of Mycobacterium fortuitumcutaneous infections acquired from whirlpool footbaths, also calledfootspas, was investigated at a nail salon in northern California. Over100 pedicure customers had prolonged boils on the lower legs that leftscars when healed. In the investigation, the area behind the screen ofthe recirculation inlet in each of 10 footspas at the nail salon wasswabbed and recovered strains of M. fortuitum from all 10. Isolates from3 footbaths and 14 patients were indistinguishable by pulsed-field gelelectrophoresis and by multilocus enzyme electrophoresis.

Before this outbreak, M. fortuitum and other rapidly growingmycobacteria (RGM) caused localized cutaneous infections but usually ina healthcare-associated setting with surgical or clinical devicescontaminated with water from the hospital or from the municipal watersystem. In the nail salon outbreak, it was suspected that themycobacteria entered the footspas through the municipal tap water andthrived in the large amount of organic debris accumulated behind thefootspa recirculation screens. However, cultures of tap water at thatnail salon later in the investigation yielded RGM in the M.chelonae-abscessus group but not M. fortuitum.

Since RGM are commonly found in municipal water systems, and since thenail care business is a $6 billion and growing industry in this country,it was hypothesized that similar whirlpool footbath-associated RGMinfections occurred sporadically but went unnoticed. Soon after thehealth communities were alerted to this outbreak, 3 cases of lowerextremity RGM infections associated with 2 different nail salons weredocumented from southern California.

Little has been published on the prevalence of mycobacteria in whirlpoolfootbaths. To determine the prevalence of nontuberculous mycobacteria inthis common nail salon equipment, a mycobacteriologic survey of footspasin nail salons in California was conducted from November to December2000.

Mycobacteria were isolated from virtually all pedicure spas surveyed,the sole exception being the footspa that had only been in service for11 days. Mycobacteria were recovered whether or not disinfectants werereportedly used and whether or not debris was visible behind therecirculation screen. Addtionally the recirculation screen was found tohave the highest level of overall bacteria. Likely due to the continuedexposure to the bulk water for the recirculation process. In someembodiments an antimicrobial coating is applied to the recirculationscreen and/or other components of the jet by the manufacturer and/or aspart of the routine cleaning process of the pedicure or whirlpool bathmaintence between customers. As both pipe (interior and exterior pipesystems as decribed by B. Munde in U.S. Pat. No. 5,230,842, which isincorporated by reference as if fully set forth herein) pipeless (U.S.Pat. Nos. 4,853,987; 5,414,878; 5,587,023, which are incorporated byreference as if fully set forth herein) and traditional foot baths havepropellers, screens and jets, the coating can be used for any pedicurebath system and all components.

RGM, M. fortuitum in particular, were the most frequently isolatedmycobacteria. The survey suggests that potentially pathogenicmycobacteria are widespread in these footspas across California. Theseorganisms most likely were introduced into the footspas through themunicipal water supply, where they colonized parts of the spas andprobably the plumbing. Given that these whirlpool footbaths arewidespread in California but similar infections known to date are rare,the presence of such mycobacteria alone may not be sufficient to causepedicure customers to get cutaneous infections from using these spas.The 2000 outbreak investigation noted an unusually large amount ofdebris behind the footspa recirculation screens, which might haveprovided a niche for mycobacteria to colonize and proliferate to largenumbers. In that outbreak, customers who shaved their legs before usingthese implicated footspas were at higher risk for furunculosis thanthose who did not. However, some customers in that outbreak wereinfected even though they reportedly did not shave their legs beforeusing the pedicure spas. Thus, while the widespread presence ofpotentially pathogenic mycobacteria in footspas has been documented, therisk for infection remains unclear.

Nonetheless, the findings documented the ubiquitous presence ofpotentially pathogenic mycobacteria among footspas of nail salons inCalifornia. The 2000 outbreak might have been a warning of what mayhappen again if this emerging infection is not adequately addressed. In2004, a case report documented 2 cases of M. mageritense furunculosisassociated with using footbaths at a nail salon in Georgia.

The California Board of Barbering and Cosmetology adopted newregulations in May 2001 requiring nail salons to follow specificcleaning and disinfection procedures to ensure that their footspaequipment is properly cleaned and maintained.

In some embodiments, compositions comprising bridged polycycliccompounds may be used to form antimicrobial coatings on devices andsystems associated with personal care and/or personal care facilities(e.g., nail and/or hair salons). Examples of personal care itemsinclude, but are not limited to, footbaths, footspas, scissors, cuticlefiles, clippers, etc.

Portions of personal care devices may be treated by the manufacturerduring production with an antimicrobial coating (e.g., the filter screenof a water pump in a footbath) and/or an end user of the device maytreat the portion themselves. In some embodiments, an end user maypurchase a kit to treat a personal care device or a portion of it. Kitare described in more detail in the Medical Device section herein.

In some embodiments a pedicure tub liner (as described by F. Sherif,et.al. in patent application U.S. 20040199994 which is incorporated byreference as if fully set forth herein) may be treated by themanufacturer or the personal care professional with antimicrobialcoating

In some embodiments, elements used within an antimicrobial coatings asdescribed herein is association with other applications or elsewhereherein (e.g., under the “Matrices” heading) may also be incorporatedinto a composition for coating a portion of a personal care article ordevice.

EXAMPLES

Having now described the invention, the same will be more readilyunderstood through reference to the following example(s), which areprovided by way of illustration, and are not intended to be limiting ofthe present invention.

General Experimental: All manipulations were carried out using Schlenktechnique under nitrogen atmosphere. Ethyl alcohol, denatured, reagentgrade, anhydrous, was purchased from EMD. Dimethylformamide (DMF),99.8%, anhydrous, was purchased from Acros Organics. Both were usedwithout further purification. Tris(2-aminoethyl)amine, 1-bromohexane,1-bromooctane, 1-bromodecane, 1-bromododecane, 1-bromohexadecane,1-bromobutane, benzylbromide and methyliodide were purchased from AcrosOrganics and distilled before use. Terephthaldicarboxaldehyde waspurchased from Acros Organics and sublimed before use. Sodiumborohydride and sodium carbonate were purchased from Acros Organics andused without further purification. NMR analysis was performed on a JEOLEclipse⁺ 400 instrument.

Synthesis of Several Examples of Bridged Polycyclic Compounds:

Synthesis of 202 and 204: To a 3000 mL, 3-neck round bottom flask wasadded terephthaldicarboxaldehyde (16.1 g, 120 mmoles) and the flaskfitted with a reflux condenser, addition funnel and thermocouple. Thenethyl alcohol (2000 mL) was added and the temperature controller set to78 ° C. About 10 minutes after the reaction solution temperature reached78 ° C., tris(2-aminoethyl)amine (11.7 g, 12.0 mL, 80.0 moles) was addedby syringe. After about 1 h the heat was removed and the reactionsolution allowed to cool. When the reaction solution temperature droppedbelow 35 ° C., sodium borohydride (9.08 g, 240 mmoles) was added and thereaction solution stirred for about 14 h at room temperature. Analysisof intermediate 202 was obtained by isolation of a sample of thereaction solution before sodium borohydride addition. Work up of 204:The reaction solution was filtered and the volatiles were removed byvacuum transfer. Then 1.0 M NaOH (250 mL) and dichloromethane (150 mL)were added. After mixing the phases were separated and the aqueous layerwas extracted with dichloromethane (2×75 mL). The organic was combined,washed with water (2×100 mL), dried over sodium sulfate and thevolatiles removed to leave the product as a white slightly waxy powder(22.1 g, 36.9 mmoles, 92.3% yield). Analysis of 202: ¹H NMR (400 MHz,CD₂Cl₂, δ): 2.74, 3.73 (s, 24H, NCH₂CH₂NCHC₆H₄), 7.15 (s, 12H,NCH₂CH₂NCHC₆H₄), 8.12 (s, 6H, NCH₂CH₂NCHC₆H₄). ESI-MS (m/z): [M+H]⁺ 587.Analysis of 204: ¹H NMR (400 MHz, CD₂Cl₂, δ): 2.61, 2.76 (m, 24H,NCH₂CH₂NHCH₂C₆H₄), 3.62 (s, 12H, NCH₂CH₂NHCH₂C₆H4), 6.84 (s, 12H,NCH₂CH₂NHCH₂C₆H₄). ESI-MS (m/z): [M+H]⁺ 599.

Synthesis of 206a: To a 100 mL flask was added 204 (8.00 g, 13.4 mmoles)and ethyl alcohol (8.4 mL). Upon stirring for about an hour sodiumcarbonate (9.37 g, 88.2 mmoles) was added followed by 1-bromohexane(14.6 g, 12.4 mL, 88.2 mmoles) and the reaction flask fitted with areflux condenser. The solution was refluxed on a thermostat controlledoil bath set to 95 ° C. for about 14 h. Then the heat was removed andthe reaction solution was cooled to room temperature. Work Up of 206a:The volatiles were removed by vacuum transfer, then the crude productwas combined with 1.0 M NaOH (150 mL) and dichloromethane (50 mL). Thephases were separated and the aqueous extracted with dichloromethane(2×50 mL). The organic phases were combined, washed with water (2×50mL), dried over sodium sulfate and the volatiles removed to leave alight greenish-yellow oil (13.5 g, 12.2 mmoles, 91.3% yield). Analysisof 206a: ¹H NMR (400 MHz, CD₂Cl₂, δ): 0.83-0.93 (m, 18H,N{CH₂CH₂N[CH₂(CH₂)₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃]CH₂CH₂}₃N), 1.19-1.46(m, 48H, N{CH₂CH₂N[CH₂(CH₂)₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃]CH₂CH₂}₃N),2.28-2.54 (m, 36H,N{CH₂CH₂N[CH₂(CH₂)₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃]CH₂CH₂}₃N), 3.28-3.64(m, 12H, N{CH₂CH₂N[CH₂(CH₂)₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃]CH₂CH₂}₃N),7.00-7.35 (m, 12H,N{CH₂CH₂N[CH₂(CH₂)₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃]CH₂CH₂}₃N). ESI-MS(m/z): [M+H]⁺ 1104.

Synthesis of 113a: To the flask containing the product 206a (13.5 g,12.2 mmoles) was added DMF (240 mL). Then methyl iodide (17.3 g, 7.60ml, 122 mmoles) was added and the reaction solution was heated with athermostat controlled oil bath set to 70 ° C. After being heated forabout 14 h, the heat was removed and the reaction solution cooled toroom temperature. Work Up of 113a: The solution was divided between two1000 mL flasks and ethyl acetate (770 mL) was added to each flask andthe solution stirred for 1 h. Then the supernatant was removed byfiltration. The precipitate was washed with ethyl acetate (3×60 mL) andthe volatiles were removed by vacuum transfer leaving an off whitepowder (24.4 g, 10.9 mmoles, 89.3% yield). Analysis of 113a: ¹H NMR (400MHz, DMF-d₇, δ): 0.81-0.84 (m, 18H,CH₃N{CH₂CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂CH₂}₃NCH₃),1.20-2.10 (m, 48H,CH₃N{CH₂CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂CH₂}₃NCH₃),3.05-4.05 (m, 54H,CH₃N{CH₂CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂CH₂}₃NCH₃),4.40-5.20 (m, 18H,CH₃N{CH₂CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂CH₂}₃NCH₃),7.50-8.15 (m, 12H,CH₃N{CH₂CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂C₆H₄CH₂N[CH₂(CH₂)₄CH₃](CH₃)CH₂CH₂}₃NCH₃).ESI-MS (m/z): [M-I]⁺ 2111, [M-2I]²⁺ 992, [M-Me-2I]⁺ 1971.

Synthesis of 206b: Using the procedure for synthesis of 206a with1-bromooctane in place of 1-bromohexane produced 206b in 96.9% yield.Analysis of 206b: ¹H NMR (400 MHz, CD₂Cl₂, δ): 0.83-0.89 (m, 18H,N{CH₂CH₂N[CH₂(CH₂)₆CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₆CH₃]CH₂CH₂}₃N), 1.23-1.43(m, 72H, N{CH₂CH₂N[CH₂(CH₂)₆CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₆CH₃]CH₂CH₂}₃N),2.28-2.54 (m, 36H,N{CH2CH₂N[CH₂(CH₂)₆CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₆CH₃]CH₂CH₂}₃N), 3.28-3.63(m, 12H, N{CH₂CH₂N[CH₂(CH₂)₆CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₆CH₃]CH₂CH₂}₃N),7.00-7.35 (m, 12H,N{CH₂CH₂N[CH₂(CH₂)₆CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₆CH₃]CH₂CH₂}₃N). ESI-MS(m/z): [M+H]⁺ 1272.

Synthesis of 113b: Using the procedure for synthesis for 113a with 206bin place of 206a produced 113b in 76.8% yield. Analysis of 113b: ESI-MS(m/z): [M-I]⁺ 2280, [M-2I]²⁺ 1076, [M-Me-2I]⁺ 2139.

Synthesis of 206c: Using the procedure for synthesis of 206a with1-bromodecane in place of 1-bromohexane produced 206c in 96.2% yield.Analysis of 206c: ¹H NMR (400 MHz, CD₂Cl₂, δ): 0.85-0.89 (m, 18H,N{CH₂CH₂N[CH₂(CH₂)₈CH₃]CH₂CAHCH₂N[CH₂(CH₂)₈CH₃]CH₂CH₂}³N), 1.24-1.44 (m,96H, N{CH₂CH₂N[CH₂(CH₂)₈CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₈CH₃]CH₂CH₂}₃N),2.29-2.56 (m, 36H,N{CH₂CH₂N[CH₂(CH₂)₈CH₃]CH₂C₆H₄CH,N[CH₂(CH₂)₈CH₃]CH₂CH₂}₃N), 3.28-3.64(m, 12H, N{CH₂CH₂N[CH₂(CH₂)₈CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₈CH₃]CH₂CH₂CH₂}₃N),6.95-7.35 (m, 12H,N{CH₂CH₂N[CH₂(CH₂)₈CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₈CH₃]CH₂CH₂}₃N). ESI-MS(m/z): [M+H]⁺ 1441.

Synthesis of 113c: Using the procedure for synthesis of 113a with 206cin the place of 206a produced 113c in 78.0% yield. Analysis of 113c:ESI-MS (m/z): [M-I]⁺ 2449, [M-2I]²⁺ 1161, [M-Me-2I]⁺ 2307.

Synthesis of 206d: Using the procedure for synthesis of 206a with1-bromododecane in place of 1-bromohexane produced 206d in 99.2% yield.Analysis of 206d: ¹H NMR (400 MHz, CD₂Cl₂, δ): 0.86-0.90 (m, 18H,N{CH₂CH₂N[CH₂(CH₂)₁₀CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₀CH₃]CH₂CH₂}₃N), 1.26-1.44(m, 120H, N{CH₂CH₂N[CH₂(CH₂)₁₀CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₀CH₃]CH₂CH₂}₃N),2.30-2.57 (m, 36H,N{CH₂CH₂N[CH₂(CH₂)₁₀CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₀CH₃]CH₂CH₂}₃N), 3.28-3.64(m, 12H, N{CH₂CH₂N[CH₂(CH₂)₁₀CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₀CH₃]CH₂CH₂}₃N),6.95-7.33 (m, 12H,N{CH₂CH₂N[CH₂(CH₂)₁₀CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₀CH₃]CH₂CH₂}₃N). ESI-MS(m/z): [M+H]⁺ 1610.

Synthesis of 113d: Using the procedure for synthesis of 113a with 206din the place of 206a produced 113d in 61.0% yield. Analysis of 113d:ESI-MS (m/z): [M-2Me-4I]²⁺ 1103, [M-3Me-5I]²⁺ 1032, [M-5Me-81]³⁺ 551.

Synthesis of 113e: To the flask containing the product 206a (13.8 g,12.5 mmoles) was added DMF (31 mL). Then benzyl bromide (21.4 g, 14.9ml, 125 mmoles) was added and the reaction solution was heated with athermostat controlled oil bath set to 80 ° C. After being heated forabout 14 h, the heat was removed and the reaction solution cooled toroom temperature. Work Up of 113e: The solution was transferred into a1000 mL flask, ethyl acetate (250 mL) was added and the solution stirredfor 30 min. Then the supernatant was removed by filtration. Theprecipitate was washed with ethyl acetate (3×60 mL) and the volatileswere removed by vacuum transfer leaving an off white powder (19.4 g,7.86 mmoles, 63.9% yield). Analysis of 113e: ESI-MS (m/z): [M-2Br]²⁺1156, [M-Bz-2Br]⁺ 2222, [M-Bz-3Br]²⁺ 1071.

Synthesis of 113f: Using the procedure for synthesis of 113e with 206din place of 206a produced 113f in 51.4% yield. Analysis of 113f: ESI-MS(m/z): [M-Bz-3Br]²⁺ 1323, [M-Bz4Br]³⁺856, [M-3Bz4Br]⁺ 2385.

Synthesis of 206g: Using the procedure for synthesis of 206a with1-bromohexadecane in place of 1-bromohexane produced 206 g in 100%yield. Analysis of 206g: ¹H NMR (400 MHz, CD₂Cl₂, δ): 0.85-0.88 (m, 18H,N {CH₂CH₂N[CH₂(CH₂)₁₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₄CH₃]CH₂CH₂}₃N), 1.22-1.42(m, 168H, N{CH₂CH₂N[CH₂(CH₂)₁₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₄CH₃]CH₂CH₂}₃N),2.28-2.78 (m, 36H, N{CH₂CH₂N[CH₂(CH₂)₁₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₄CH₃]CH₂CH₂}₃N), 3.28-3.65(m, 12H, N {CH₂CH₂N[CH₂(CH₂)₁₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₄CH₃]CH₂CH₂}₃N),6.85-7.33 (m, 12H,N{CH₂CH₂N[CH₂(CH₂)₁₄CH₃]CH₂C₆H₄CH₂N[CH₂(CH₂)₁₄CH₃]CH₂CH₂}₃N). ESI-MS(m/z): [M+H]⁺ 1946.

Synthesis of 206h: To a 100 mL flask was added 204 (1.01 g, 1.69 mmoles)and DMF (8.4 mL). Upon stirring for about an hour sodium carbonate (1.08g, 10.2 mmoles) was added followed by 1-bromobutane (1.39 g, 1.09 mL,10.2 mmoles) and the reaction flask fitted with a reflux condenser. Thesolution was refluxed on a thermostat controlled oil bath set to 70 ° C.for about 14 h. Then the heat was removed and the reaction solution wascooled to room temperature. Work Up of 206h: The volatiles were removedby vacuum transfer, then the crude product was combined with 1.0 M NaOH(25 mL) and dichloromethane (25 mL). The phases were separated and theaqueous extracted with dichloromethane (2×25 mL). The organic phaseswere combined, washed with water (2×25 mL), dried over sodium sulfateand the volatiles removed to leave a light greenish-yellow oil (1.18 g,1.26 mmoles, 74.5% yield). Analysis of 206h: ESI-MS (m/z): [M+H]⁺ 936and related peaks.

Synthesis of 113h: To the flask containing the product 206h (0.661 g,0.653 mmoles) was added DMF (6.5 mL). Then methyl iodide (0.927 g, 0.406ml, 6.53 mmoles) was added and the reaction solution was heated with athermostat controlled oil bath set to 50 ° C. After being heated forabout 14 h, the heat was removed and the reaction solution cooled toroom temperature. Work Up of 113h: To the reaction solution was addedethyl acetate (80 mL) and the solution stirred for 90 min. The solutionwas filtered and the precipitate washed with ethyl acetate (3×10 mL) andthe volatiles removed by vacuum transfer leaving an off white powder(1.30 g, 0.626 mmoles, 95.9% yield). Analysis of 113h: ESI-MS (m/z):[M-21]²⁺ 992 and related peaks.

Synthesis of a bridged polycyclic compound with a surface linker:

General Experimental: All manipulations were carried out using Schlenktechnique under nitrogen atmosphere. Acetonitrile, anhydrous, waspurchased from EMD. The 2-ethyl oxazoline was purchased from AcrosOrganics and distilled before use from phosphorous pentoxide.Methyl-4-(bromomethyl)benzoate and potassium iodide were purchased fromAldrich and used without further purification. Cryptand 206a wassynthesized as disclosed previously. NMR analysis was performed on aJEOL Eclipse+400 instrument at Acorn NMR, Inc. in Livermore, Calif. MSanalysis was performed at Scripps Center for Mass Spectrometry in LaJolla, Calif.

Synthesis of 208: To a 50 mL flask was addedmethyl-4-(bromomethyl)benzoate (1.13 g, 4.95 mmol), acetonitrile (5 mL),potassium iodide (8.22 mg) and 2-ethyl oxazoline (5.0 mL, 4.91 g, 49.5mmoles). The flask was fitted with a reflux condenser and placed in anoil bath set to 82 ° C. for 14 h. After heating the reaction solutionwas cooled to room temperature. For polymer analysis, a 0.5 mL sample ofthe reaction solution was stirred in 5 mL of water overnight at roomtemperature before the volatiles removed by vacuum transfer at roomtemperature. Analysis of 208: MALDI-TOF MS (m/z): [M+H₂O+H]⁺ 860.6(n=7), [M+H₂O+H]⁺ 960.0 (n=8), [M+H₂O+H]⁺ 1058.7 (n=9), [M+H₂O+H]⁺1157.8 (n=10).

Synthesis of 210: To a 50 mL flask was added 206a (50 mg, 0.0534mmoles), 208 (0.0540 mL, 0.0267 mmoles, 0.495 M) and 1.0 mL of CH₃CN.The flask was heated on an 80 ° C. oil bath for 3 days. After heatingthe reaction solution was cooled to room temperature and the volatilesremoved by vacuum transfer. Analysis of 210: MALDI-TOF MS (m/z): forR¹=(CH₂)₅CH₃; [M+H]⁺ 1554 (6×R¹ where R¹=(CH₂)₅CH₃, n=3), [M+H]⁺ 1653(6×R¹where R¹=(CH₂)₅CH₃, n=4), [M+H]+1752 (6×R¹ where R¹=(CH₂)₅CH₃,n=5), and [M+H]⁺ 1243 (R═H, n=4), [M+H]⁺ 1342 (R═H, n=5), [M+H]⁺ 1441(R═H, n=6).

Further Example of a Synthesis of a Bridged Polycyclic Compound with aSurface Linker:

Formulation of Coating Composition Containing C6C1 Alkylated BridgedPolycyclic Compound

General Experimental: Poly vinyl alcohol (PVA), 80% hydrolized, typicalmw 9,000-10,000, poly methyl methacrylate (PMMA), typical mw 120,000 andpoly(methylmethacrylate-co-butylmethacrylate), (PMMABMA), typical mw75,000 were purchased from Aldrich and used without furtherpurification. Acetone and 1-butanol were also purchased from Aldrich andused without further purification. Active ingredient C6C1 alkylatedcryptand salt was synthesized as disclosed previously. Mixing waspreformed by an IKA “RW16 Basic” stirrer equipped with a “R1300Dissolver Stirrer” impeller for larger scale and for smaller scale thesolutions were magnetically stirred.

Formulation of PVA in Water Example: A 10% PVA in water is used forexample although formulations between 1 and 20% PVA in water wereproduced (the preferred formulation range is 15 to 20% PVA in water).Water (900 mL) was stirred and PVA (100 g) was added in four portionswith 10 minute separation between each portion. The solution was thenstirred until clear and colorless. The foam was removed with a papertowel and the solution transferred to a glass bottle for storage.

Formulation of PVA/PMMA in Water Example: A sample of the 15% PVA watersolution (50 mL) was added to a small bottle and PMMA (50 mg, 0.1%) wasadded. The solution was magnetically stirred for 24 h resulting in aclear homogeneous solution.

Formulation of PVA/PMMABMA in Water Example: A 15% PVA in water is usedfor example although formulations between 1and 20% PVA in water wereproduced (the preferred formulation range is 15 to 20% PVA in water).Water (360 mL) was stirred and PVA (60 g, 0.1%) was added in fourportions with 10 minute separation between each portion. Then PMMABMA (2g) was added and the solution was then stirred until clear andcolorless.

Formulation of the Active Ingredient in PVA/Water Solution Example: Asample of the 10% PVA/water solution (50 mL) was added to a small bottleand the active ingredient (1.5 g) previously dissolved in DMF (3.0 mL)was added. The solution was magnetically stirred for 24 h resulting in aclear homogeneous solution.

Formulation of the Active Ingredient in PVA/PMMA/Water Solution Example:A sample of the 15% PVA/0.1% PMMA/water solution (0.5 mL) was added to avial containing 7.5 mg of active ingredient and the solution stirred for5 min. Then 0.050 mL of 1-butanol was added and the solution stirred for1 day.

Formulation of the Active Ingredient in PVA/PMMA/Water Solution Example:A sample of the 15% PVA/0.1% PMMA/water solution (0.5 mL) was added to avial containing 7.5 mg of active ingredient and the solution stirred for5 min. Then 0.050 mL of acetone was added and the solution stirred for 1day.

Formulation of the Active Ingredient in PVA/PMMABMA/Water SolutionExample: A sample of the 15% PVA/0.1% PMMABMA/water solution (0.5 mL)was added to a vial containing 7.5 mg of active ingredient and thesolution stirred for 5 min. Then 0.050 mL of 1-butanol was added and thesolution stirred for I day.

Formulation of the Active Ingredient in PVA/PMMABMA/Water SolutionExample: A sample of the 15% PVA/0.1% PMMABMA/water solution (0.5 mL)was added to a vial containing 7.5 mg of active ingredient and thesolution stirred for 5 min. Then 0.050 mL of acetone was added and thesolution stirred for 1 day.

In the examples above DMF, 1-butanol and/or acetone were used as asolvent. Other solvents for this system are dimethyl sulfoxide,isopropanol, pentanol, hexanol, propylene glycol, ethylene glycol,ethylene glycol 2-ethylhexyl ether, di(ethylene glycol)2-ethylhexylether, ethylene glycol butyl ether, di(ethylene glycol) hexyl ether,3-ethylhexanol, hexanol, 1,4-butanediol, ethanol and the like.

Other additives for this formulation: PMMA, sodium borate, boric acid,potassium tetrafluoroborate, sodium tetrafluoroborate, EDTA, disodiumEDTA, metal oxides, silica and the like.

EXAMPLES: Time Kill Test Assay for Antimicrobial Agents

Test Substance Preparation: A 1.0 mL volume of DMSO was placed into asterile vessel and vortex mixed for 10-15 seconds. Immediately followingthe mixing of the DMSO, 0.025 g of the test substance powder was addedto the sterile vessel and vortex mixed for 10-15 seconds to make a stocksolution. The stock solution was then combined with 9.9 mL of filtersterilized deionized water, vortex mixed for 10-15 seconds and 0.1 mL ofthe solution was discarded resulting in a total volume of 9.9 mL and atest substance concentration of 0.25 mg/mL.

Experimental Design: A suspension of bacterial cells was exposed to thetest substance for specified contact times. After exposure, an aliquotof the suspension was transferred to a neutralizing subculture media andassayed for survivors. Appropriate purity, sterility, initial suspensionpopulation control and neutralization controls were performed.

Test Organisms: Test organisms included Staphylococcus aureus andEscherichia coli in a growth medium of tryptic soy agar with 5% sheepblood, as well as, Aspergillus niger in a growth medium of sabouraudagar modified.

Time Kill Test Assay for 113h vs. 113b: Under the conditions of thisstudy, 113h, demonstrated a 98.5% or 1.828 log reduction ofStaphylococcus aureus survivors after a 5 minute exposure, a 92.5% or1.13 log reduction after a 10 minute exposure, a 99.5% or 2.33 logreduction after a 30 minute exposure, a >99.8% or 2.92 log reductionafter a 1 hour exposure, a 99.999% or 5.0 log reduction after a 6 hourexposure, a 99.999% or 5.7 log reduction after a 24 hour exposure whentested at room temperature (24° C.).

Under the conditions of this study, 113b, demonstrated a 99.1% or 2.029log reduction of Staphylococcus aureus survivors after a 5 minuteexposure, a 94.2% or 1.24 log reduction after a 10 minute exposure, a99.1% or 2.06 log reduction after a 30 minute exposure, a 99.8% or 2.63log reduction after a 1 hour exposure, a 99.99% or 4.35 log reductionafter a 6 hour exposure, a >99.999% or >5.7 log reduction after a 24hour exposure when tested at room temperature (24° C.).

Under the conditions of this study, 113h, demonstrated a 77.7% or 0.66log reduction of Escherichia coli survivors after a 5 minute exposure, a86.6% or 0.88 log reduction after a 10 minute exposure, a 82.9% or 0.77log reduction after a 30 minute exposure, a 91.1% or 1.06 log reductionafter a 1 hour exposure, a 98.5% or 1.83 log reduction after a 6 hourexposure, a 99.7% or 2.58 log reduction after a 24 hour exposure whentested at room temperature (24° C.).

Under the conditions of this study, 113b, demonstrated a 89.0% or 0.96log reduction of Escherichia coli survivors after a 5 minute exposure, a84.9% or 0.83 log reduction after a 10 minute exposure, a 93.7% or 1.21log reduction after a 30 minute exposure, a 94.6% or 1.27 log reductionafter a 1 hour exposure, a 99.0% or 2.00 log reduction after a 6 hourexposure, a 99.5% or 2.28 log reduction after a 24 hour exposure whentested at room temperature (24° C.).

Under the conditions of this study, 113h, demonstrated no percent or logreduction of Aspergillus niger following 5 minute, 10 minute, 30 minute,1 hour, 6 hour, and 24 hour exposure times when tested at roomtemperature (24° C.).

Under the conditions of this study, 113b, demonstrated a 47.0% or 0.28log reduction of Aspergillus niger survivors after a 5 minute exposure,a 38.9% or 0.22 log reduction after a 10 minute exposure, a 47.6% or0.28 log reduction after a 30 minute exposure, a 48.1% or 0.29 logreduction after a 1 hour exposure, a 47.6% or 0.28 log reduction after a6 hour exposure, a 27.8% or 0.14 log reduction after a 24 hour exposurewhen tested at room temperature (24° C.).

Time Kill Test Assay for 113a: Under the conditions of this study, 113a,demonstrated a 98.6% or 1.856 log reduction of Staphylococcus aureussurvivors after a 5 minute exposure, a 99.9% or 3.97 log reduction aftera 10 minute exposure, a >99.999% or >5.8 log reduction after a 30minute, 1 hour, 6 hour, and 24 hour exposure period when tested at roomtemperature (20° C.).

Under the conditions of this study, 113a, demonstrated a 96.3% or 1.42log reduction of Escherichia coli survivors after a 5 minute exposure, a97.7% or 1.64 log reduction after a 10 minute exposure, a 99.3% or 2.14log reduction after a 30 minute exposure, a 99.6% or 2.35 log reductionafter a 1 hour exposure, a 99.9% or 3.660 log reduction after a 6 hourexposure, a >99.9999% or >6.0 log reduction after a 24 hour exposurewhen tested at room temperature (20° C.).

Under the conditions of this study, 113a, demonstrated a 18.3% or 0.09log reduction of Aspergillus niger survivors after a 5 minute exposure,a 38.0% or 0.21 log reduction after a 10 minute exposure, a 28.2% or0.14 log reduction after a 30 minute exposure, a 39.4% or 0.22 logreduction after a 1 hour exposure, no reduction after a 6 hour exposure,a 25.4% or 0.13 log reduction after a 24 hour exposure when tested atroom temperature (20° C.).

Time Kill Test Assay for 113a vs. 113d: Under the conditions of thisstudy, 113a, demonstrated a 97.9% or 1.68 log reduction ofStaphylococcus aureus survivors after a 5 minute exposure, a 99.9% or3.22 log reduction after a 10 minute exposure, a 99.999% or 5.2 logreduction after a 30 minute, a >99.999% or >5.5 log reduction after a 1hour, 6 hour, and 24 hour exposure period when tested at roomtemperature (22° C.).

Under the conditions of this study, 113d, demonstrated a 82.5% or 0.76log reduction of Staphylococcus aureus survivors after a 5 minuteexposure, a 84.1% or 0.80 log reduction after a 10 minute exposure, a96.8% or 1.50 log reduction after a 30 minute, a 99.8% or 2.72 logreduction after a 1 hour, and a >99.999% or >5.5 log reduction after a 6hour, and 24 hour exposure period when tested at room temperature (22°C.).

Under the conditions of this study, 113a, demonstrated a 92.3% or 1.12log reduction of Escherichia coli survivors after a 5 minute exposure, a91.5% or 1.07 log reduction after a 10 minute exposure, a 93.7% or 1.21log reduction after a 30 minute exposure, a 95.5% or 1.35 log reductionafter a 1 hour exposure, a 99.4% or 2.23 log reduction after a 6 hourexposure, a 99.9% or 3.58 log reduction after a 24 hour exposure whentested at room temperature (22° C.).

Under the conditions of this study, 113d, demonstrated a 38.7% or 0.22log reduction of Escherichia coli survivors after a 5 minute exposure, a80.5% or 0.72 log reduction after a 10 minute exposure, a 78.7% or 0.68log reduction after a 30 minute exposure, a 89.3% or 0.98 log reductionafter a 1 hour exposure, a 98.0% or 1.70 log reduction after a 6 hourexposure, a 99.9% or 3.07 log reduction after a 24 hour exposure whentested at room temperature (22° C.).

Under the conditions of this study, 113a, demonstrated no reduction ofAspergillus niger survivors after a 5 minute, a 10 minute, a 30 minute,and a 1 hour exposure, a 2.2% or 0.01 log reduction after a 6 hourexposure, a 135.5% or 0.19 log reduction after a 24 hour exposure whentested at room temperature (22° C.).

Under the conditions of this study, 113d, demonstrated no reduction ofAspergillus niger survivors after a 5 minute exposure, a 15.4% or 0.07log reduction after a 10 minute, a 14.3% or 0.07 log reduction after a30 minute exposure, a 3.3% or 0.02 log reduction after a 1 hourexposure, a 4.4% or 0.02 log reduction after a 6 hour exposure, a 11.3%or 0.05 log reduction after a 24 hour exposure when tested at roomtemperature (22° C.).

Residual Surface Time Kill Test Assay for 113a vs. 113e: Under theconditions of this study, 113a, demonstrated a 94.9% or 1.32 logreduction of Aspergillus niger survivors after a 1 hour exposure, a95.0% or 1.30 log reduction after a 6 hour, and a 98.8% or 1.93 logreduction after a 24 hour exposure times when tested at room temperature(21.5° C.).

Under the conditions of this study, 113e, demonstrated a 92.7% or 1.15log reduction of Aspergillus niger survivors after a 1 hour exposure, a93.8% or 1.21 log reduction after a 6 hour exposure, a 89.6% or 0.98 logreduction after a 24 hour exposure when tested at room temperature(21.5° C.).

In this patent, certain U.S. patents, U.S. patent applications, andother materials (e.g., articles) have been incorporated by reference.The text of such U.S. patents, U.S. patent applications, and othermaterials is, however, only incorporated by reference to the extent thatno conflict exists between such text and the other statements anddrawings set forth herein. In the event of such conflict, then any suchconflicting text in such incorporated by reference U.S. patents, U.S.patent applications, and other materials is specifically notincorporated by reference in this patent.

Further modifications and alternative embodiments of various aspects ofthe invention will be apparent to those skilled in the art in view ofthis description. Accordingly, this description is to be construed asillustrative only and is for the purpose of teaching those skilled inthe art the general manner of carrying out the invention. It is to beunderstood that the forms of the invention shown and described hereinare to be taken as the presently preferred embodiments. Elements andmaterials may be substituted for those illustrated and described herein,parts and processes may be reversed, and certain features of theinvention may be utilized independently, all as would be apparent to oneskilled in the art after having the benefit of this description of theinvention. Changes may be made in the elements described herein withoutdeparting from the spirit and scope of the invention as described in thefollowing claims.

1. A method of coating an oral surface, comprising: applying one or morebridged polycyclic compounds to at least a portion of an oral surface,wherein at least one of the bridged polycyclic compounds has a generalstructure:

wherein each R¹ is independently N, N⁺R³, or N⁺H; wherein each R² isindependently an alkyl group, a substituted alkyl group, or an alkene;wherein each R³ is independently an alkyl group, a substituted alkylgroup, an aryl group, a substituted aryl group, a heterocycle group, asubstituted heterocycle group, an alkene, an ether, apolyethyleneglycol, a benzyl group, a hydrogen, a hydrophilic group, ora polyethyleneimine; wherein each R⁴ is independently a substituted arylgroup; wherein Z comprises at least one bridge, wherein at least one ofthe bridges is —R² —N⁺R³ ₂—R⁴—N⁺R³ ₂—R²— or —R²—NR³—R⁴—NR³—R²—, andwherein each bridge independently couples R¹ to R¹; wherein the arylgroup is a phenyl, a naphthyl, a biphenyl, a diphenylmethyl, or abenzophenone; wherein the substituted alkyl group comprises at least onesubstituent and wherein each substituent is independently an aryl, anacyl, an alkyl, a halogen, an alkylhalo, a hydroxy, an amino, an alkoxy,an alkylamino, an acylamino, an acyloxy, an aryloxy, an aryloxyalkyl, amercapto, a saturated cyclic hydrocarbon, an unsaturated cyclichydrocarbon, and/or a heterocycle; wherein the substituted aryl group isa phenyl having at least one substituent, a naphthyl having at least onesubstituent, a biphenyl having at least one substituent, adiphenylmethyl having at least one substituent, or a benzophenone havingat least one substituent, and wherein each substituent is independentlyan alkyl, an aryl, an acyl, a halogen, an alkylhalo, a hydroxy, anamino, an alkoxy, an alkylamino, an acylamino, an acyloxy, an aryloxy,an aryloxyalkyl, a thioether, a heterocycle, a saturated cyclichydrocarbon, and/or an unsaturated cyclic hydrocarbon; wherein thesubstituted heterocycle group comprises at least one substituent andwherein each substituent is independently an alkyl, an aryl, an acyl, ahalogen, an alkylhalo, a hydroxy, an amino, an alkoxy, an alkylamino, anacylamino, an acyloxy, an aryloxy, an aryloxyalkyl, a thioether, aheterocycle, a saturated cyclic hydrocarbon, and/or an unsaturatedcyclic hydrocarbon; wherein each of the hydrophilic groups independentlycomprises a hydroxyl, a methoxy, a carboxylic acid, an ester of acarboxylic acid, an amide, an amino, a cyano, an isocyano, an ammoniumsalt, a sulfonium salts, a phosphonium salt, a mono-alkyl substitutedamino groups, a di-alkyl substituted amino group, a polypropyleneglycol,a polyethylene glycol, an epoxy group, an acrylate, a sulfonamide, anitro, a —OP(O)(OCH₂CH₂N⁺R³R³R³)O⁻, a guanidinium, an aminate, anacrylamide, a pyridinium, a piperidine, a polymethylene chainssubstituted with an alcohol, a carboxylate, an acrylate, or amethacrylate, an alkyl chain having internal amino or substituted aminogroups comprising internal —NH—, —NC(O)R³—, or —NC(O)CH═CH₂—groups, apolycaprolactone, a polycaprolactone diol, a poly(acetic acid), apoly(vinyl acetate), a poly(2-vinyl pyridine), a cellulose ester, acellulose hydroxylether, a poly(L-lysine hydrobromide), a poly(itaconicacid), a poly(maleic acid), a poly(styrenesulfonic acid), apoly(aniline), or a poly(vinyl phosphonic acid); and wherein X comprisesone or more negatively charged counter ions; and forming anantimicrobial coating over at least a portion of the oral surface. 2.The method of claim 1, wherein at least one of the bridged polycycliccompounds comprises at least four quaternary ammonium moieties.
 3. Themethod of claim 1, wherein at least one quaternary ammonium moietydefining at least one cyclic group of one or more of the bridgedpolycyclic compounds further comprises an alkyl group, a substitutedalkyl group, an aryl group, a heterocycle group, a substitutedheterocycle group, or a substituted aryl group.
 4. The method of claim1, wherein at least one quaternary ammonium moiety defining at least onecyclic group of one or more of the bridged polycyclic compounds furthercomprises an alkyl group, a substituted alkyl group, an aryl group, or asubstituted aryl group and an alkyl group, a substituted alkyl group, anaryl group, or a substituted aryl group.
 5. The method of claim 1,wherein at least one quaternary ammonium moiety defining at least onecyclic group of one or more of the bridged polycyclic compounds furthercomprises a C6 alkyl group or a C6 substituted alkyl group and a methylgroup or a benzyl group.
 6. The method of claim 1, wherein at least oneof the bridged polycyclic compound has a general structure (I):


7. The method of claim 1, wherein at least one X is iodine.
 8. Themethod of claim 1, wherein at least one X is bromine or chlorine.
 9. Themethod of claim 1, wherein at least one of the bridged polycycliccompound has a general structure (IV):

wherein at least one R³ is a benzyl group, and wherein at least one R³is a C5-C7 alkyl group or a C5-C7 substituted alkyl group; and whereinat least one R⁴ is an aryl group or a substituted aryl group.
 10. Themethod of claim 1, wherein at least one of the bridged polycycliccompound has a general structure (IVa):

wherein at least one R³ is a benzyl group, wherein at least one R³ is aC5-C7 alkyl group or a C5-C7 substituted alkyl group; wherein at leastone R⁴ is an aryl group or a substituted aryl group, and wherein Mcomprises one or more guest molecules associated with one or moreportions of compound (IVa).
 11. The method of claim 1, wherein the oralsurface comprises at least a portion of a tooth surface, at least aportion of a gum, at least a portion of soft tissue, or at least aportion of a dental fixture.
 12. The method of claim 1, wherein the oneor more bridged polycyclic compounds are part of a composition, whereinthe composition further comprises a at least one gelator such that thecomposition is gel.
 13. The method of claim 1, wherein the one or morebridged polycyclic compounds are part of a composition, and wherein thecomposition further comprises at least one polymer or polymerizablecompound, and further comprising using the composition as a bondingagent.
 14. The method of claim 1, wherein the one or more bridgedpolycyclic compounds are part of a composition, and wherein thecomposition further comprises at least one polymer or polymerizablecompound, and further comprising using the composition as a resincement.
 15. The method of claim 1, wherein the one or more bridgedpolycyclic compounds are part of a composition, and wherein thecomposition further comprises at least one polymer or polymerizablecompound, and further comprising using the composition as a sealant. 16.The method of claim 1, wherein the one or more bridged polycycliccompounds are part of a composition, and wherein the composition furthercomprises at least one polymer or polymerizable compound, and furthercomprising applying one or more of the bridged polycyclic compounds asat least a portion of a varnish.
 17. The method of claim 1, wherein theone or more bridged polycyclic compounds are part of a composition, andwherein the composition further comprises at least one polymer orpolymerizable compound, and further comprising using the composition asa resin.
 18. The method of claim 1, wherein at least one R³ comprises aguanidinium.
 19. The method of claim 1, wherein at least one of thecyclic groups comprises an amide moiety coupled to the cyclic group. 20.The method of claim 1, wherein at least one R³ comprises a quaternaryammonium moiety.
 21. The method of claim 1, wherein the oral surfacecomprises the oral surface of a dog or a cat.
 22. The method of claim 1,wherein at least one of the bridged polycyclic compound has a generalstructure:


23. The method of claim 22, wherein R² is —(CH₂)₂—.
 24. The method ofclaim 22, wherein R⁴ is a substituted aryl group, and wherein thesubstituted aryl group comprises —(CH₂)-phenyl-(CH₂)—.
 25. The method ofclaim 22, wherein at least one R³ is a substituted aryl group.
 26. Themethod of claim 22, wherein at least one R³ comprises a substituted arylgroup, wherein at least one of the substituted aryl group's substituentscomprises a guanidinium group.
 27. The method of claim 22, wherein atleast one R³ comprises a substituted aryl group, wherein at least one ofthe substituted aryl group's substituents is a halogen, and wherein atleast one of the substituted aryl group's substituents comprises aguanidinium group.
 28. The method of claim 1, wherein at least one ofthe bridged polycyclic compound has a general structure:

wherein each R¹ is independently N, N⁺H, or N⁺R³; wherein at least oneR³ comprises a substituted aryl group, wherein at least one of thesubstituted aryl group's substituents is a halogen, and wherein at leastone of the substituted aryl group's substituents comprises a guanidiniumgroup; and wherein X comprises one or more negatively charged counterions.
 29. The method of claim 1, wherein the one or more bridgedpolycyclic compounds are part of a composition, wherein the compositionfurther comprises a solvent.
 30. The method of claim 1, wherein the oneor more bridged polycyclic compounds are part of a composition, whereinthe composition further comprises a solvent, and wherein the solventcomprises water and an alcohol based solvent.
 31. The method of claim 1,wherein the one or more bridged polycyclic compounds are part of acomposition, wherein the composition further comprises a polymer and/ora polymerizable compound.
 32. The method of claim 1, wherein at leastone R³ comprises a substituted aryl group.
 33. The method of claim 1,wherein at least one R³ comprises a substituted aryl group, wherein atleast one of the substituted aryl group's substituents comprises aguanidinium group.
 34. The method of claim 1, wherein each R³ isindependently an alkyl group, a substituted alkyl group, an aryl group,a substituted aryl group, a heterocycle group, a substituted heterocyclegroup, an alkene, an ether, a polyethyleneglycol, a benzyl group, ahydrogen, a hydrophilic group, or a polyethyleneimine and wherein atleast one alkyl group comprises a C5-C7 alkyl group.
 35. The method ofclaim 1, wherein the one or more bridged polycyclic compounds are partof a composition, wherein the composition further comprises a solvent,and wherein the solvent comprises water.
 36. The method of claim 1,wherein the one or more bridged polycyclic compounds are part of acomposition, wherein the composition further comprises a solvent, andwherein the solvent comprises an alcohol based solvent.
 37. The methodof claim 1, wherein the one or more bridged polycyclic compounds arepart of a composition, wherein the composition further comprises asolvent and a polymer, and wherein the solvent comprises water and analcohol based solvent.
 38. The method of claim 28, wherein the one ormore bridged polycyclic compounds are part of a composition, wherein thecomposition further comprises a solvent, and wherein the solventcomprises water.
 39. The method of claim 28, wherein the one or morebridged polycyclic compounds are part of a composition, wherein thecomposition further comprises a solvent, and wherein the solventcomprises an alcohol based solvent.
 40. The method of claim 28, whereinthe one or more bridged polycyclic compounds are part of a composition,wherein the composition further comprises a solvent, and wherein thesolvent comprises water and an alcohol based solvent.
 41. The method ofclaim 28, wherein the one or more bridged polycyclic compounds are partof a composition, wherein the composition further comprises a solventand a polymer, and wherein the solvent comprises water and an alcoholbased solvent.
 42. A method of coating an oral surface of a cat or adog, comprising: applying one or more bridged polycyclic compounds to atleast a portion of an oral surface of a cat or a dog, wherein at leastone of the bridged polycyclic compounds has a general structure:

wherein each R¹ is independently N, N⁺R³, or N⁺H; wherein each R² isindependently an alkyl group, a substituted alkyl group, or an alkene;wherein each R³ is independently an alkyl group, a substituted alkylgroup, an aryl group, a substituted aryl group, a heterocycle group, asubstituted heterocycle group, an alkene, an ether, apolyethyleneglycol, a benzyl group, a hydrogen, a hydrophilic group, ora polyethyleneimine; wherein each R⁴ is independently a substituted arylgroup; wherein Z comprises at least one bridge, wherein at least one ofthe bridges is —R²—N⁺R³ ₂—R⁴—N⁺R³ ₂—R²— or —R²—NR³—R⁴—NR³—R²—, andwherein each bridge independently couples R¹ to R¹; wherein the arylgroup is a phenyl, a naphthyl, a biphenyl, a diphenylmethyl, or abenzophenone; wherein the substituted alkyl group comprises at least onesubstituent and wherein each substituent is independently an aryl, anacyl, an alkyl, a halogen, an alkylhalo, a hydroxy, an amino, an alkoxy,an alkylamino, an acylamino, an acyloxy, an aryloxy, an aryloxyalkyl, amercapto, a saturated cyclic hydrocarbon, an unsaturated cyclichydrocarbon, and/or a heterocycle; wherein the substituted aryl group isa phenyl having at least one substituent, a naphthyl having at least onesubstituent, a biphenyl having at least one substituent, adiphenylmethyl having at least one substituent, or a benzophenone havingat least one substituent and wherein each substituent is independentlyan alkyl, an aryl, an acyl, a halogen, an alkylhalo, a hydroxy, anamino, an alkoxy, an alkylamino, an acylamino, an acyloxy, an aryloxy,an aryloxyalkyl, a thioether, a heterocycle, a saturated cyclichydrocarbon, and/or an unsaturated cyclic hydrocarbon; wherein thesubstituted heterocycle group comprises at least one substituent andwherein each substituent is independently an alkyl, an aryl, an acyl, ahalogen, an alkylhalo, a hydroxy, an amino, an alkoxy, an alkylamino, anacylamino, an acyloxy, an aryloxy, an aryloxyalkyl, a thioether, aheterocycle, a saturated cyclic hydrocarbon, and/or an unsaturatedcyclic hydrocarbon; wherein each of the hydrophilic groups independentlycomprises a hydroxyl, a methoxy, a carboxylic acid, an ester of acarboxylic acid, an amide, an amino, a cyano, an isocyano, an ammoniumsalt, a sulfonium salts, a phosphonium salt, a mono-alkyl substitutedamino groups, a di-alkyl substituted amino group, a polypropyleneglycol,a polyethylene glycol, an epoxy group, an acrylate, a sulfonamide, anitro, a —OP(O)(OCH₂CH₂N⁺R³R³R³)O⁻, a guanidinium, an aminate, anacrylamide, a pyridinium, a piperidine, a polymethylene chainssubstituted with an alcohol, a carboxylate, an acrylate, or amethacrylate, an alkyl chain having internal amino or substituted aminogroups comprising internal —NH—, —NC(O)R³—, or —NC(O)CH═CH₂— groups, apolycaprolactone, a polycaprolactone diol, a poly(acetic acid), apoly(vinyl acetate), a poly(2-vinyl pyridine), a cellulose ester, acellulose hydroxylether, a poly(L-lysine hydrobromide), a poly(itaconicacid), a poly(maleic acid), a poly(styrenesulfonic acid), apoly(aniline), or a poly(vinyl phosphonic acid); and wherein X comprisesone or more negatively charged counter ions; and forming anantimicrobial coating over at least a portion of the oral surface. 43.The method of claim 11, wherein at least one of the bridged polycycliccompounds comprises at least four quaternary ammonium moieties.
 44. Themethod of claim 11, wherein at least one of the bridged polycycliccompound has a general structure (I):


45. The method of claim 11, wherein at least one X is iodine.
 46. Themethod of claim 11, wherein at least one X is bromine or chlorine. 47.The method of claim 11, wherein the oral surface comprises at least aportion of a tooth surface, at least a portion of a gum, at least aportion of soft tissue, or at least a portion of a dental fixture. 48.The method of claim 11, wherein the one or more bridged polycycliccompounds are part of a composition, wherein the composition furthercomprises a at least one gelator such that the composition is gel. 49.The method of claim 11, wherein the one or more bridged polycycliccompounds are part of a composition, and wherein the composition furthercomprises at least one polymer or polymerizable compound, and furthercomprising using the composition as a bonding agent.
 50. The method ofclaim 11, wherein the one or more bridged polycyclic compounds are partof a composition, and wherein the composition further comprises at leastone polymer or polymerizable compound, and further comprising using thecomposition as a resin cement.
 51. The method of claim 11, wherein theone or more bridged polycyclic compounds are part of a composition, andwherein the composition further comprises at least one polymer orpolymerizable compound, and further comprising using the composition asa sealant.
 52. The method of claim 11, wherein the one or more bridgedpolycyclic compounds are part of a composition, and wherein thecomposition further comprises at least one polymer or polymerizablecompound, and further comprising applying one or more of the bridgedpolycyclic compounds as at least a portion of a varnish.
 53. The methodof claim 11, wherein the one or more bridged polycyclic compounds arepart of a composition, and wherein the composition further comprises atleast one polymer or polymerizable compound, and further comprisingusing the composition as a resin.
 54. The method of claim 11, wherein atleast one R³ comprises a guanidinium.
 55. The method of claim 11,wherein at least one R³ comprises a quaternary ammonium moiety.
 56. Themethod of claim 11, wherein at least one of the bridged polycycliccompound has a general structure:


57. The method of claim 11, wherein at least one of the bridgedpolycyclic compound has a general structure:

wherein each R¹ is independently N, N⁺H, or N⁺R³; wherein at least oneR³ comprises a substituted aryl group, wherein at least one of thesubstituted aryl group's substituents is a halogen, and wherein at leastone of the substituted aryl group's substituents comprises a guanidiniumgroup; and wherein X comprises one or more negatively charged counterions.
 58. The method of claim 57, wherein the one or more bridgedpolycyclic compounds are part of a composition, wherein the compositionfurther comprises a solvent, and wherein the solvent comprises water.59. The method of claim 57, wherein the one or more bridged polycycliccompounds are part of a composition, wherein the composition furthercomprises a solvent, and wherein the solvent comprises an alcohol basedsolvent.
 60. The method of claim 57, wherein the one or more bridgedpolycyclic compounds are part of a composition, wherein the compositionfurther comprises a solvent, and wherein the solvent comprises water andan alcohol based solvent.
 61. The method of claim 57, wherein the one ormore bridged polycyclic compounds are part of a composition, wherein thecomposition further comprises a solvent and a polymer, and wherein thesolvent comprises water and an alcohol based solvent.
 62. The method ofclaim 11, wherein the one or more bridged polycyclic compounds are partof a composition, wherein the composition further comprises a solvent.63. The method of claim 11, wherein the one or more bridged polycycliccompounds are part of a composition, wherein the composition furthercomprises a solvent, and wherein the solvent comprises water.
 64. Themethod of claim 11, wherein the one or more bridged polycyclic compoundsare part of a composition, wherein the composition further comprises asolvent, and wherein the solvent comprises an alcohol based solvent. 65.The method of claim 11, wherein the one or more bridged polycycliccompounds are part of a composition, wherein the composition furthercomprises a solvent, and wherein the solvent comprises water and analcohol based solvent.
 66. The method of claim 11, wherein the one ormore bridged polycyclic compounds are part of a composition, wherein thecomposition further comprises a solvent and a polymer, and wherein thesolvent comprises water and an alcohol based solvent.
 67. The method ofclaim 11, wherein the one or more bridged polycyclic compounds are partof a composition, wherein the composition further comprises a polymerand/or a polymerizable compound.
 68. The method of claim 11, wherein atleast one R³ comprises a substituted aryl group.
 69. The method of claim11, wherein at least one R³ comprises a substituted aryl group, whereinat least one of the substituted aryl group's substituents comprises aguanidinium group.
 70. The method of claim 11, wherein each R³ isindependently an alkyl group, a substituted alkyl group, an aryl group,a substituted aryl group, a heterocycle group, a substituted heterocyclegroup, an alkene, an ether, a polyethyleneglycol, a benzyl group, ahydrogen, a hydrophilic group, or a polyethyleneimine and wherein atleast one alkyl group comprises a C5-C7 alkyl group.